Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial.

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Low-frequency transcutaneous electrical stimulation has been proposed as a potential adjunctive therapy, but its efficacy in clinical settings is uncertain. Methods In this randomized controlled trial, 32 patients with isolated traumatic digital nerve injuries underwent surgical neurorrhaphy at a tertiary care hospital. Participants were randomly allocated to an intervention group (n = 16) or sham group (n = 16). The intervention consisted of a single postoperative session of square-pulsed, biphasic transcutaneous electrical stimulation at 20 Hz for 1 hour. The sham group received identical conditions without active stimulation. After stimulation, patients underwent physiotherapy sessions for three months. Sensory recovery was assessed using Semmes-Weinstein monofilament testing and two-point discrimination at baseline, 1 week, 1 month, and 3 months postoperatively. Results Both groups showed progressive sensory improvement throughout follow-up, approaching normal values at 3 months. No statistically significant differences were observed between groups in any outcome measure. Confidence intervals for group comparisons overlapped, and no clinically meaningful differences were detected. No adverse effects were reported. Conclusions In this model, a single postoperative session of low-frequency transcutaneous electrical stimulation did not significantly enhance sensory recovery after digital nerve repair. Further research with varied stimulation protocols, repeated sessions, or extended follow-up may be warranted to clarify its potential role in peripheral nerve regeneration. Level of Evidence Therapeutic Level I. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-1222/v3", "name": "Effects of transcutaneous electrical stimulation on peripheral nerve..." } } ] } Home Browse Effects of transcutaneous electrical stimulation on peripheral nerve... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Mattos EdSRd, Guedes A, Zana Y et al. Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.12688/f1000research.169801.3 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Revised Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] Enilton de Santana Ribeiro de Mattos https://orcid.org/0000-0003-2039-9744 1,2 , Alex Guedes https://orcid.org/0000-0001-7013-7107 1,2 , Yossi Zana 3 , [...] Paulo Itamar Ferraz Lessa 4 , César Romero Antunes Júnior https://orcid.org/0000-0003-1701-5279 1,2 , Eduardo Silva Reis Barreto https://orcid.org/0009-0008-4688-8857 1,2 , Abrahão Fontes Baptista https://orcid.org/0000-0001-7870-3820 5 Enilton de Santana Ribeiro de Mattos https://orcid.org/0000-0003-2039-9744 1,2 , Alex Guedes https://orcid.org/0000-0001-7013-7107 1,2 , [...] Yossi Zana 3 , Paulo Itamar Ferraz Lessa 4 , César Romero Antunes Júnior https://orcid.org/0000-0003-1701-5279 1,2 , Eduardo Silva Reis Barreto https://orcid.org/0009-0008-4688-8857 1,2 , Abrahão Fontes Baptista https://orcid.org/0000-0001-7870-3820 5 PUBLISHED 09 May 2026 Author details Author details 1 Orthopedics and Traumatology Research Group, Federal University of Bahia (UFBA), Salvador, Bahia, 40110-100, Brazil 2 Faculty of Medicine of Bahia, Federal University of Bahia, Salvador, Bahia, 40026-010, Brazil 3 Graduate Program of Neuroscience, Federal University of ABC, São Bernardo do Campo, São Paulo, 09606-045, Brazil 4 Bahia State University, Salvador, State of Bahia, 41150-000, Brazil 5 Laboratory of Functional Neuromodulation and Pain, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Rio de Janeiro, 21941-853, Brazil Enilton de Santana Ribeiro de Mattos Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Project Administration, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Alex Guedes Roles: Methodology, Resources, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Yossi Zana Roles: Data Curation, Resources, Supervision, Validation, Writing – Original Draft Preparation Paulo Itamar Ferraz Lessa Roles: Methodology, Resources, Supervision, Validation, Writing – Original Draft Preparation César Romero Antunes Júnior Roles: Data Curation, Writing – Original Draft Preparation Eduardo Silva Reis Barreto Roles: Data Curation, Writing – Original Draft Preparation Abrahão Fontes Baptista Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Resources, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background Sensory recovery following digital nerve neurorrhaphy is often incomplete, and strategies to enhance regeneration remain under investigation. Low-frequency transcutaneous electrical stimulation has been proposed as a potential adjunctive therapy, but its efficacy in clinical settings is uncertain. Methods In this randomized controlled trial, 32 patients with isolated traumatic digital nerve injuries underwent surgical neurorrhaphy at a tertiary care hospital. Participants were randomly allocated to an intervention group (n = 16) or sham group (n = 16). The intervention consisted of a single postoperative session of square-pulsed, biphasic transcutaneous electrical stimulation at 20 Hz for 1 hour. The sham group received identical conditions without active stimulation. After stimulation, patients underwent physiotherapy sessions for three months. Sensory recovery was assessed using Semmes-Weinstein monofilament testing and two-point discrimination at baseline, 1 week, 1 month, and 3 months postoperatively. Results Both groups showed progressive sensory improvement throughout follow-up, approaching normal values at 3 months. No statistically significant differences were observed between groups in any outcome measure. Confidence intervals for group comparisons overlapped, and no clinically meaningful differences were detected. No adverse effects were reported. Conclusions In this model, a single postoperative session of low-frequency transcutaneous electrical stimulation did not significantly enhance sensory recovery after digital nerve repair. Further research with varied stimulation protocols, repeated sessions, or extended follow-up may be warranted to clarify its potential role in peripheral nerve regeneration. Level of Evidence Therapeutic Level I. READ ALL READ LESS Keywords Peripheral nerve regeneration, Digital nerve injury, Transcutaneous electrical stimulation, TENS, Randomized controlled trial, Digital nerve Corresponding Author(s) Abrahão Fontes Baptista ( [email protected] ) Close Corresponding author: Abrahão Fontes Baptista Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2026 Mattos EdSRd et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Mattos EdSRd, Guedes A, Zana Y et al. Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.12688/f1000research.169801.3 ) First published: 06 Nov 2025, 14 :1222 ( https://doi.org/10.12688/f1000research.169801.1 ) Latest published: 09 May 2026, 14 :1222 ( https://doi.org/10.12688/f1000research.169801.3 ) Revised Amendments from Version 2 This version includes several revisions to improve methodological clarity and interpretation of the findings. We clarified the anatomical targeting of the stimulation protocol, specifying that electrode placement was individualized according to the injured digit and surgical repair site, while the median nerve motor threshold was used only as an operational reference for stimulation intensity. We also added numerical between-group estimates, including unadjusted mean differences and 95% confidence intervals for SWM, s2PD, CSS, and PDI at the 3-month assessment, to support interpretation of the null findings beyond p-values alone. The Discussion and Study limitations sections were expanded to address the sensitivity of SWM and s2PD, the possibility of ceiling effects, the limited generalizability of isolated digital nerve injuries to more complex nerve lesions, the absence of a dose–response framework, the potential masking effect of postoperative rehabilitation, and the limitations of a 3-month follow-up. We also clarified that the findings should be interpreted as showing no detectable clinical advantage of this specific surface PES protocol, rather than definitive evidence against electrical stimulation as a broader strategy for peripheral nerve regeneration. This version includes several revisions to improve methodological clarity and interpretation of the findings. We clarified the anatomical targeting of the stimulation protocol, specifying that electrode placement was individualized according to the injured digit and surgical repair site, while the median nerve motor threshold was used only as an operational reference for stimulation intensity. We also added numerical between-group estimates, including unadjusted mean differences and 95% confidence intervals for SWM, s2PD, CSS, and PDI at the 3-month assessment, to support interpretation of the null findings beyond p-values alone. The Discussion and Study limitations sections were expanded to address the sensitivity of SWM and s2PD, the possibility of ceiling effects, the limited generalizability of isolated digital nerve injuries to more complex nerve lesions, the absence of a dose–response framework, the potential masking effect of postoperative rehabilitation, and the limitations of a 3-month follow-up. We also clarified that the findings should be interpreted as showing no detectable clinical advantage of this specific surface PES protocol, rather than definitive evidence against electrical stimulation as a broader strategy for peripheral nerve regeneration. See the authors' detailed response to the review by Johannes Heinzel See the authors' detailed response to the review by Nish Mohith Kurukuti READ REVIEWER RESPONSES Introduction The human hand is a rich sensory and motor multifunctional tool with dexterous control to perform essential manipulation tasks. 1 Peripheral nerve injuries, especially of the upper limb, can result in severe disability and reduced quality of life. 2 – 4 Several strategies 5 – 8 including the use of neurotrophic factors, stem cell therapy, 9 , 10 and electrical stimulation, 11 have been investigated to promote peripheral nerve regeneration as well as functional recovery after these traumas. 12 Electrical stimulation has also been considered as an ancillary to surgical repair, and its effects on nerve recovery has been the focus of several studies. 13 – 25 It is to be noted that the characteristics and regenerative potential of peripheral nerves differ markedly depending on the location and type of lesion. 26 Differences in digital nerve lesions compared with more proximal and mixed lesions are described. 26 , 27 Digital nerves are almost exclusively sensory, and injuries to these nerves, properly repaired, generally have shorter regeneration distances and can serve as a model for evaluating the effects of transcutaneous peripheral electrical stimulation (PES), delivered through surface electrodes (commonly referred to as TENS). 27 By contrast, proximal nerve injuries, or nerve injuries with larger gaps to overcome, may be more difficult to completely regenerate, given the increased length for axonal growth and the complexity of motor and sensory functional recovery. 28 There are different ways to deliver the PES such as implanted electrodes, 15 , 16 percutaneous electrostimulation 17 , 18 (acupuncture needles inserted into the skin and connected to an electric current generator), intraoperative electrostimulation, 19 – 23 thin-film wireless implantable nerve stimulators, 24 and surface electrodes. 25 The use of transcutaneous surface electrodes is a non-invasive, practical, and simple option, avoiding the reactions provoked by implant surgery or percutaneous stimulation. 29 Based on these considerations, we hypothesized that a brief, early postoperative session of transcutaneous PES could modulate biological mechanisms associated with nerve regeneration following digital neurorrhaphy. This hypothesis was grounded on evidence from experimental and clinical studies showing that short-duration electrical stimulation applied soon after nerve repair may enhance activity-dependent regenerative processes. 23 , 30 In the present study, we intentionally adapted these principles to a non-invasive and clinically feasible protocol, consisting of a single 1-hour session of surface stimulation delivered at motor threshold within 24 hours after surgery. The stimulation protocol (20 Hz, 1 hour) was selected based on the findings of Al-Majed et al. (2000), 19 which identified this window as optimal for the upregulation of BDNF and TrkB mRNA. Although the digital nerve is sensory, the intensity was calibrated to the motor threshold of the median nerve to ensuring supramaximal recruitment of large-diameter A-beta sensory fibers, which share similar electrical thresholds with A-alpha motor fibers. Although this approach aimed to reproduce, in a transcutaneous manner, stimulation parameters previously associated with regenerative benefits, its biological effectiveness in purely sensory digital nerves remains unclear. Therefore, we conducted a randomized clinical trial to investigate whether this specific surface PES protocol could influence sensory recovery, cold sensitivity, and pain-related disability in patients undergoing digital nerve repair. Methods This double-blind, randomized, controlled clinical trial was conducted at a general hospital in Bahia, Brazil, from December 19, 2020, to June 10, 2022. The study was prospectively registered in the Brazilian Clinical Trials Registry (ReBEC) on December 18, 2020 (registration number: U1111-1259-1998; available at: https://ensaiosclinicos.gov.br/rg/RBR-8xn3qq5 ). Ethical approval was obtained from the Research Ethics Committee of the Faculty of Medicine of Bahia, and the study protocol was published 31 in advance to ensure methodological transparency and compliance with the Declaration of Helsinki. 32 Participants Adult patients aged 18 to 60 years with an acute, non-segmental digital nerve injury of the hand were eligible for inclusion if surgical repair was successfully performed within two weeks of injury. Exclusion criteria comprised the presence of metal implants at the surgical site, history of seizures, use of a cardiac pacemaker, local infection or skin lesions at the intervention site, associated bone or tendon injuries, and any pre-existing neuropathies. Interventions All patients underwent standardized microsurgical neurorrhaphy under ultrasound-guided axillary block, with epineural approximation using 2 to 4 nylon 8-0 sutures to align nerve fascicles and minimize trauma. Within 24 hours after surgery, participants were randomly allocated to one of two groups. The stimulation parameters were chosen based on previous studies related to nerve regeneration and patient safety. 11 , 14 , 15 , 19 Group A (Surgery + PES) received one hour of transcutaneous electrical stimulation using the Neurodyn II device (Ibramed, Brazil), delivering a square-pulsed, biphasic, symmetrical current at 20 Hz with a 0.4 ms pulse width. Stimulation intensity was standardized using the median nerve motor threshold as an operational reference, rather than as the anatomical stimulation target. Electrode placement was individualized for the injured digit and the surgical repair site. In all participants, two 1 × 1 cm silicone-carbon gel electrodes were positioned proximal and distal to the neurorrhaphy, along the presumed course of the repaired digital nerve. Therefore, the intervention was anatomically directed to the injured digital nerve branch, although selective and equivalent recruitment of the repaired nerve across all digits cannot be fully confirmed. Group B (Surgery + sham PES) underwent an identical setup with the same device, electrode positioning, and duration, but after an initial perceptible activation, the device output was reduced to zero for the remainder of the session ( Figure 2 ). A certified physiotherapist, blinded to the group allocation, supervised the rehabilitation protocol. Sessions were remotely monitored via electronic platforms such as WhatsApp or Skype. Patients underwent a hand sensory re-education program based on the approach proposed by Dellon & Jabaley (1982), 33 focused on hand sensory re-education over 3-month period. Participants were also encouraged to perform complementary exercises in a home-based program. Figure 1. CONSORT 2010 flowchart diagram of patient screening, intervention, and follow-up. *Intention-to-treat (ITT) analysis. Figure 2. Model of a repaired digital nerve injury of the index finger and the electrodes placement. Randomization, allocation concealment, and blinding Patients were randomly assigned in a 1:1 ratio to Group A (surgery + PES) or Group B (surgery + sham) using an electronic randomization sequence generated with the website randomization.com (available at the time of study planning). Allocation concealment was ensured through centralized management by an independent researcher who was the only person with access to the randomization list. A physiotherapist, blinded to group assignment, administered all stimulation sessions using identical devices with the same electrode placement and duration. For sham sessions, the device was initially activated to produce perceptible stimulation cues before being set to zero output. Although real PES could induce subtle muscle contractions, the identical device design and protocol helped maintain blinding for both participants and the administering physiotherapist. Assessment schedule All patients were evaluated in person by the same surgeon responsible for both the surgical procedure and postoperative follow-up. Assessments were scheduled at four time points: (1) pre-intervention; (2) one-week post-intervention; (3) one-month post-intervention (including ongoing rehabilitation sessions); (4) three months post-intervention (upon completion of all 20 rehabilitation sessions). The three-month follow-up period was selected based on the expected timeframe for peripheral nerve regeneration over short distances (2 to 6 cm), assuming an average axonal growth rate of 1 to 3 mm per day. 34 Outcome measures The primary outcome was sensory recovery of digital nerves following microsurgical neurorrhaphy, assessed using quantitative sensory tests. Specifically, the Semmes-Weinstein Monofilament (SWM) test and the static two-point discrimination (s2PD) test were applied during four scheduled in-person evaluations. Outcome differences between the two groups (intervention vs. sham) were analyzed post-randomization. The SWM test, a crucial marker of functional recovery, assesses perception of pressure thresholds related to peripheral reinnervation. 35 During the test, participants rested their hands on a table and closed their eyes. In three trials, we applied scored probes perpendicularly to the pulp side of the affected finger for 1 to 1.5 seconds. A positive response in at least two of three trials indicated the sensory threshold. 23 The secondary outcome included self-reported measures of cold sensitivity and pain-related functional disability. These were evaluated using the Cold Sensitivity Severity Scale (CSS) 36 and the Pain Disability Index (PDI), 37 both validated tools for assessing postoperative sensory complaints and pain impact on daily life, aimed to measure improvements in terms of cold sensitivity and pain disability in social functions for individuals who underwent neurorrhaphy of digital nerves in the hand. We used two patient-reported outcome questionnaires: the Cold Sensitivity Severity Scale (CSS) 36 and the Pain Disability Index (PDI). 37 These patient-reported outcomes were assessed only at the 3-month follow-up, after completion of the rehabilitation protocol. The s2PD test serves as an established assessment tool for evaluating tactile gnosis. 2 , 38 It measures the ability to distinguish between two nearby points touching the skin, ensuring they are truly distinct rather than perceived as a single point. The test estimates the minimum distance necessary for the patient to perceive the two pressure points as separate contacts. 39 It reflects the degree of innervation in a specific skin area. The Medical Research Council classification, modified by Mackinnon & Dellon, allows grouping based on different value ranges related to the sensitive recovery threshold 35 , 40 ( Table 2 ). Table 1. Baseline patient characteristics. Electrical stimulation (n = 16) Sham (n = 16) Mean age (range in years) 36.6 (18–57) 34.2 (21–58) Male sex ( no. [%]) 9 (56) 12 (75) Right-handed ( no. [%]) 13 (81) 14 (87) Injury to the dominant hand (no. [%]) 6 (38) 8 (50) Injury to the radial digital nerve ( no. [%]) 9 (56) 7 (44) Injured finger Thumb (n=8) 4 4 Index (n=9) 5 4 Midlle (n=2) 1 1 Ringer (n=4) 1 3 Litlle (n=9) 5 4 Diabetes 1 0 Smoker 2 4 Table 2. Modified HIGHET classification reproduced from a study by Dunlop et al. (2019). Sensory recovery Highet s2PD m2PD Recovery of sensibility Failure S0 No recovery of sensibility in the autonomous zone of the nerve Poor S1 Recovery of deep cutaneous pain sensibility S1+ Recovery of superficial pain and some touch sensibility S2 Recovery of superficial pain sensibility S2+ As with S2, but with over response S3 >15 mm >7 mm Recovery of pain and touch sensibility with no over response Good S3+ 7–15 mm 4–7 mm As in S3, but good localization of the stimulus but imperfect recovery of 2PD Excellent S4 2–6 mm 2–3 mm Complete sensory recovery The CSS offers a reliable way to assess cold sensitivity. In cases like amputation or nerve damage, hypersensitivity can occur and lead to significant disability. The CSS consists of four questions related to cold-induced symptoms. The total score provides the cold-sensitivity severity score. The PDI comprises a seven-item questionnaire evaluating how pain affects various aspects of daily life. Each item is rated from 0 (no disability) to 10 (total disability), and the final score (ranging from 0 to 70) reflects the level of disability due to pain. The PDI has demonstrated consistency, validity, and reliability in studies related to nerve damage. 37 Sample size The sample size was estimated based on effect size data reported by Gordon et al. (2010). 23 We calculated the sample size considering a repeated measures analysis of variance (ANOVA) test, accounting for interactions between and within factors. The effect size, as reported by Gordon et al. (2010), 23 was 0.26. Additionally, we set an alpha-type error of 5%, a statistical power of 80%, and worked with two groups and three measures. Adjustments were applied to account for correlations among repeated measures (correlation coefficient = 0.5) and a non-sphericity correction factor of 1.0 (assuming compound symmetry). Based on these assumptions, the minimum required sample was calculated to be 26 participants. To account for potential losses, we increased the sample size by 20%, resulting in a final sample of 32 patients (16 per group). Statistical analysis The data were evaluated in a paired and non-paired way through within and between-group comparisons. For within-group evaluations, repeated measures ANOVA or the Friedman test was applied, followed by the Student–Newman–Keuls post hoc test. For between-group comparisons, one-way ANOVA or the Kruskal-Wallis test was used, followed by the Student-Newman-Keuls post hoc test. Specifically, repeated measures ANOVA was used for normally distributed SWM and s2PD data across time points, while the Friedman test was applied when normality assumptions were not met. Between-group comparisons at each time point were performed using one-way ANOVA or Kruskal–Wallis tests accordingly. Independent samples t-tests were used for CSS and PDI comparisons at 3 months. The choice of statistical tests was based on the distribution characteristics of the data, and normality was assessed using the Shapiro-Wilk test or the nature of the data. A 95% confidence interval was considered for statistical analysis, with statistical significance set ai p < 0.05 an alpha of 5% (P < 0.05) and a power of 80%. Descriptive analysis was conducted using means and standard errors or medians and interquartile range (25 th /75 th percentiles), as appropriate to data distribution. Both measurements of the variables and the statistical analysis were performed under blinded conditions by assessors unaware of group allocation. The independent variable for both groups was the use of electric current. The dependent variables were derived from the pre- and post-treatment assessments (SWM, s2PD, CSS, and PDI). All statistical tests were performed using JASP (V0.18.3). Results Eligibility was evaluated in a total of 54 patients. Of these, 21 did not meet the inclusion criteria, and one declined to participate. Thus, 32 patients were randomized, with 16 allocated to the PES group and 16 to the sham group ( Figure 1 ). Baseline characteristics were comparable between groups, and all participants presented with severe sensory impairment on preoperative evaluation, assessed by MSW and s2PD tests ( Table 1 ). No significant differences between groups were observed during the immediate postoperative period (up to one week; p > 0.05), so subsequent statistical analyses focused on the 1- and 3-month follow-up data. Sensory outcomes improved over time in both groups, with significant changes observed between 1 and 3 months postoperatively. Repeated measures ANOVA demonstrated a significant effect of time for both SWM (p = 0.012) and s2PD (p = 0.002), indicating progressive sensory recovery in both groups. No significant group effect or group–time interaction was observed for either outcome (p > 0.05). Age showed a marginal influence on SWM outcomes (p = 0.082), becoming significant when scores were converted to needle size (p = 0.014) ( Figure 3 ). Figure 3. Sensory and patient-reported outcomes after digital nerve repair in the PES and sham groups. Top panels show mean Semmes-Weinstein monofilament thresholds (SWM, grams) and static two-point discrimination (s2PD, millimeters) at 1 and 3 months postoperatively. Both groups demonstrated progressive sensory recovery over time, with no significant differences between PES and sham. Bottom panels show Cold Sensitivity Severity Scale (CSS) and Pain Disability Index (PDI, 0–70) scores at 3 months. Error bars represent standard error of the mean. As CSS and PDI were assessed only at the 3-month follow-up, comparisons between groups were performed using an independent samples t-test at this single time point. No statistically significant differences were found for CSS (p = 0.305) or PDI (p = 0.477). However, the two scales were highly correlated (r = 0.819, p < 0.001), suggesting consistent subjective perception of disability and cold sensitivity among patients. Age was initially included as a covariate due to its known influence on nerve regeneration. To assess the robustness of the results, sensitivity analyses were performed by (1) excluding age as a covariate and (2) removing an outlier, a 57-year-old participant from the PES group with discrepant SWM values (z-score ≈ 5). In summary, patients in both groups gradually recovered sensitivity as measured by SWM and s2PD, reaching satisfactory levels at the final assessment. However, no significant treatment effect was found across time points. At 3 months, the unadjusted mean between-group difference between PES and sham was 0.10 g for SWM (95% CI, -0.94 to 1.15) and 0.79 mm for s2PD (95% CI, -0.26 to 1.83). For patient-reported outcomes, the mean between-group difference was -13.71 points for CSS (95% CI, -40.55 to 13.13) and -2.46 points for PDI (95% CI, -9.46 to 4.54) ( Figure 3 ). Importantly, these sensitivity analyses did not alter the primary conclusions of the study. Discussion This randomized controlled trial investigated the effectiveness of surface PES in promoting sensory recovery following digital nerve neurorrhaphy. Both groups exhibited a gradual recovery of sensory function over the 3-month follow-up, as measured by SWM and s2PD tests. From a theoretical perspective, electrical stimulation is thought to enhance nerve regeneration through activity-dependent mechanisms that require effective recruitment of regenerating axons and sufficient current density at the nerve site. In the present study, the transcutaneous delivery of stimulation, applied at motor threshold in a purely sensory nerve injury, may not have provided the selectivity or intensity of fiber activation necessary to trigger these mechanisms. 41 Although age showed a near-significant effect in some models, its overall influence appears limited. Cold sensitivity and pain-related disability were assessed only at the final follow-up and showed high inter-individual variability, limiting the ability to draw definitive conclusions regarding these secondary outcomes. Transcutaneous electrical stimulation holds promise in nerve regeneration, offering a non-invasive approach with potential practical benefits. 42 It can be utilized to circumvent the complications of surgical implantation or percutaneous stimulation. 43 , 44 Some research indicates that it may take up to 8 weeks for the regenerating axons to cover a distance of 25mm, and the use of PES may reduce this period. 20 , 26 Previous results demonstrated that subjects who received stimulation exhibited earlier and better outcomes around 3 months post-surgery. 26 Gordon at al. (2010) 23 conducted an innovative randomized controlled trial (RCT) of 21 patients undergoing carpal tunnel decompression surgery. Postoperative direct nerve stimulation using implanted wires (20 Hz, 4-6 volts 0.1-0.8 ms) for one hour led to earlier improvements in electrophysiological parameters when compared to controls. Simillarly, Wong et al. (2015) 26 conducted a double-blind RCT involving 31 patients with transected digital nerves and observed significantly improved sensory outcomes with PES (20 Hz, <30 V, 0.1–0.4 ms), although no differences in overall functional recovery were found. In another trial, Power et al. (2020) 45 evaluated PES following cubital tunnel decompression in 31 patients. The intervention group received a single 1-hour session of PES (20 Hz, <30 V, 0.1 ms) and demonstrated greater improvements in Motor Unit Number Estimation (MUNE) over time compared to the control group. Importantly, these studies employed direct, implanted, or intraoperative stimulation, ensuring higher current density and selective activation of nerve fibers at the repair site, conditions that differ substantially from transcutaneous stimulation and may explain the discrepancy in findings. The present findings should also be interpreted in light of the absence of a dose–response framework. This trial tested a single 1-hour session of surface PES, selected to mirror parameters previously associated with regenerative effects in experimental and clinical studies. However, neuromodulatory effects may depend on stimulation dose, timing, repetition, current density, and cumulative exposure. Therefore, the absence of benefit with this single-session protocol does not exclude the possibility that repeated sessions, different intensities, alternative timing, or longer stimulation schedules could produce different outcomes. Some studies reported adverse findings that contradict prior research that has highlighted the advantageous impact of direct current electric fields on the regeneration of peripheral nerves. 46 , 47 In the present trial, neither the s2PD nor the SWM tests demonstrated a significant enhancement in tactile receptor reinnervation in the digital pulp among patients who received PES. Given these results, the effectiveness of transcutaneous applied electrical fields in promoting in vivo peripheral nerve regeneration remains uncertain. Cold intolerance 48 and pain 49 are commonly reported sources of substantial morbidity following nerve injuries in the hand. Previous studies have associated the severity of these symptoms with the degree of sensory recovery, with poorer reinnervation correlating with more pronounced functional impairment and discomfort. 49 , 50 In the present sample, isolated digital nerve injuries were not associated with worse outcomes in terms of pain or cold intolerance, as measured by the CSS and PDI. These symptoms appear to be more commonly linked to complex cases involving finger replantation, severe vascular compromise, or proximal nerve injuries of the median or ulnar nerves. Postoperative rehabilitation following hand neurorrhaphy is considered standard of care 51 and was prescribed for all participants in this study. Withholding rehabilitation would be ethically inappropriate, as hand therapy is routinely recommended after surgery in real-world clinical settings. Omission of such care could also compromise the study’s external validity. Nevertheless, the use of structured rehabilitation in both groups may have reduced the ability to isolate the specific contribution of PES. Because sensory re-education and hand therapy are expected to promote functional recovery after neurorrhaphy, improvements driven by rehabilitation in both groups may have masked subtle additive effects of the stimulation protocol. 52 The use of a digital nerve injury model in this study presents inherent limitations regarding the generalizability of the findings. Digital nerve injuries differ substantially from proximal or mixed nerve lesions, particularly due to the shorter axonal regeneration distances and the absence of motor components. Because isolated digital nerve injuries typically show rapid and favorable recovery after repair, the short regeneration distance may have produced a ceiling effect by three months. In addition, although SWM and s2PD are widely used and clinically meaningful tools after digital nerve repair, they may have limited sensitivity to detect subtle differences in axonal regeneration, receptor reinnervation, or sensory processing. 53 – 55 Therefore, small biological effects of PES may have remained below the detection threshold of these clinical measures. Consequently, although our findings provide insight into the effects of surface PES in isolated digital sensory nerve injuries, they may not be directly applicable to more clinically challenging scenarios, such as mixed motor-sensory nerve injuries, delayed repairs, segmental defects, nerve gaps, or proximal lesions requiring longer regenerative distances. Future studies should consider the use of more complex clinical models, such as proximal or mixed nerve injuries, to better assess the potential of electrical stimulation in promoting meaningful functional recovery. Therefore, the present findings should be interpreted as evidence regarding the limitations of this specific stimulation paradigm in this clinical model, rather than as evidence against the potential usefulness of electrical stimulation as a broader therapeutic strategy for peripheral nerve regeneration. Study limitations One limitation of PES is the potential interference of the anesthetic technique with its effectiveness. Ideally, surgery should be performed under general anesthesia. A recent study in rats 56 demonstrated that the perioperative use of lidocaine significantly reduced the beneficial effects of electrical stimulation on nerve regeneration. In our study, an axillary block (far from the stimulation site) was used, and PES was applied after post-anesthetic recovery. However, a potential attenuating effect on nerve due to anesthesia cannot be completely ruled out. Current trends in hand surgery increasingly favor local or regional anesthesia, given their advantages of lower perioperative risk, faster recovery, and superior postoperative analgesia. Therefore, proposing PES as an adjunct treatment in digital nerve repair under general anesthesia (without first evaluating its use under standard anesthetic conditions) may limit its clinical applicability. Skin impedance may have resulted in insufficient current density reaching the nerve when compared to the levels achieved with implanted electrodes. 23 In addition, the short regeneration distance in isolated digital nerve injuries may have contributed to a ceiling effect, while SWM and s2PD may not have been sensitive enough to detect subtle treatment-related differences. The 3-month follow-up also limits the temporal resolution of the findings. This period captures early sensory recovery after short-distance digital nerve repair, but later outcomes at 6 to 12 months may better reflect sensory refinement, cortical reorganization, functional integration, and patient adaptation during daily hand use. Another limitation of this study is that part of the functional evaluation relied on subjective, patient-reported data. Although neurophysiological assessments can serve as sensitive tools for evaluating the severity and progression of nerve injuries in adults, their application was limited in this study. All patients had isolated digital nerve lacerations, which complicates electrophysiological interpretation due to signal contamination through volume conduction from the intact digital nerve branch on the opposite side of the finger. 26 Nevertheless, recent outcome research in the field of peripheral nerve injury has increasingly emphasized the importance of combining functional assessments with patient-reported outcomes. 57 Conclusion The specific protocol of surface PES tested in this study may not confer additional clinical benefit in isolated digital nerve injuries under standard rehabilitation conditions. No significant differences were observed in cold sensitivity or pain-related disability outcomes between the intervention and control groups. These findings suggest that, within the context of isolated digital nerve injuries, surface PES may not confer additional clinical benefit beyond standard surgical repair and rehabilitation. Further research is warranted to explore the efficacy and safety of electrical stimulation protocols in more complex nerve injury models and under varying clinical conditions. Ethical considerations This study was approved by the Research Ethics Committee of the Faculty of Medicine of Bahia (Federal University of Bahia), under protocol number 4.430.230. All procedures were conducted in accordance with the Declaration of Helsinki. The study was prospectively registered in the Brazilian Clinical Trials Registry (ReBEC) under registration number U1111-1259-1998. Consent to participate All participants provided written informed consent prior to enrollment in the study, including consent for surgical intervention, application of surface PES, and participation in follow-up assessments. Data availability All data underlying the results of this study are available within the article itself. The CONSORT 2010 checklist and flowchart associated with this trial are openly available in Figshare at https://doi.org/10.6084/m9.figshare.30120691 , under the Creative Commons CC0 license. 58 The database and project analysis are also openly available in Figshare under the Creative Commons CC0 license at https://doi.org/10.6084/m9.figshare.30350653 . 59 Additional study resources are available in Figshare, including the list of study materials https://doi.org/10.6084/m9.figshare.13636685.v1 , 60 the available facilities https://doi.org/10.6084/m9.figshare.13636694.v1 , 61 and the participant information sheet and consent form. 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Publisher Full Text Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 06 Nov 2025 ADD YOUR COMMENT Comment Author details Author details 1 Orthopedics and Traumatology Research Group, Federal University of Bahia (UFBA), Salvador, Bahia, 40110-100, Brazil 2 Faculty of Medicine of Bahia, Federal University of Bahia, Salvador, Bahia, 40026-010, Brazil 3 Graduate Program of Neuroscience, Federal University of ABC, São Bernardo do Campo, São Paulo, 09606-045, Brazil 4 Bahia State University, Salvador, State of Bahia, 41150-000, Brazil 5 Laboratory of Functional Neuromodulation and Pain, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Rio de Janeiro, 21941-853, Brazil Enilton de Santana Ribeiro de Mattos Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Project Administration, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Alex Guedes Roles: Methodology, Resources, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Yossi Zana Roles: Data Curation, Resources, Supervision, Validation, Writing – Original Draft Preparation Paulo Itamar Ferraz Lessa Roles: Methodology, Resources, Supervision, Validation, Writing – Original Draft Preparation César Romero Antunes Júnior Roles: Data Curation, Writing – Original Draft Preparation Eduardo Silva Reis Barreto Roles: Data Curation, Writing – Original Draft Preparation Abrahão Fontes Baptista Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Resources, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (3) version 3 Revised Published: 09 May 2026, 14:1222 https://doi.org/10.12688/f1000research.169801.3 version 2 Revised Published: 11 Mar 2026, 14:1222 https://doi.org/10.12688/f1000research.169801.2 version 1 Published: 06 Nov 2025, 14:1222 https://doi.org/10.12688/f1000research.169801.1 Copyright © 2026 Mattos EdSRd et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Mattos EdSRd, Guedes A, Zana Y et al. Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.12688/f1000research.169801.3 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 3 VERSION 3 PUBLISHED 09 May 2026 Revised Views 0 Cite How to cite this report: Heinzel J. Reviewer Report For: Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.5256/f1000research.200497.r483123 ) The direct URL for this report is: https://f1000research.com/articles/14-1222/v3#referee-response-483123 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 14 May 2026 Johannes Heinzel , Department of Hand-, Plastic, Reconstructive and Burn Surgery, BG Klinik Tuebingen, University of Tuebingen, Tuebingen, Baden-Wuerttemberg, Germany Approved VIEWS 0 https://doi.org/10.5256/f1000research.200497.r483123 The authors have sufficiently addressed my ... Continue reading READ ALL The authors have sufficiently addressed my concerns. I endorse publication of this manuscript. Competing Interests: No competing interests were disclosed. Reviewer Expertise: nerve regeneration, nerve surgery, functional recovery I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Heinzel J. Reviewer Report For: Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.5256/f1000research.200497.r483123 ) The direct URL for this report is: https://f1000research.com/articles/14-1222/v3#referee-response-483123 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 2 VERSION 2 PUBLISHED 11 Mar 2026 Revised Views 0 Cite How to cite this report: Heinzel J. Reviewer Report For: Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.5256/f1000research.196634.r474927 ) The direct URL for this report is: https://f1000research.com/articles/14-1222/v2#referee-response-474927 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 21 Apr 2026 Johannes Heinzel , Department of Hand-, Plastic, Reconstructive and Burn Surgery, BG Klinik Tuebingen, University of Tuebingen, Tuebingen, Baden-Wuerttemberg, Germany Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.196634.r474927 This manuscript presents a well-conducted randomized controlled trial addressing a clinically relevant question in peripheral nerve regeneration. The study is methodologically rigorous, clearly reported, and provides valuable negative findings in a field where such data remain underrepresented. I would like ... Continue reading READ ALL This manuscript presents a well-conducted randomized controlled trial addressing a clinically relevant question in peripheral nerve regeneration. The study is methodologically rigorous, clearly reported, and provides valuable negative findings in a field where such data remain underrepresented. I would like to offer several additional comments that may further strengthen the manuscript: External validity and patient selection: The inclusion of isolated, non-segmental digital nerve injuries represents a relatively favorable clinical scenario with inherently good recovery potential. While this is acknowledged, it would be helpful to more explicitly discuss how this limits generalizability to more clinically challenging cases (e.g., mixed nerves, delayed repair, or segmental defects), where adjunctive therapies may be more impactful. Dose–response considerations: The study investigates a single stimulation session. Expanding the discussion to more explicitly address the absence of a dose–response framework would help contextualize the negative findings within the broader neuromodulation literature. Rehabilitation as a potential confounder: All patients underwent structured postoperative physiotherapy, which is appropriate and ethically required. However, given its known impact on sensory recovery, a more explicit discussion of its potential to mask subtle intervention effects would be valuable. Temporal resolution of outcomes: With follow-up limited to 3 months, the study primarily captures early sensory recovery. It would be helpful to briefly discuss whether later time points (e.g., 6–12 months), particularly for cortical reorganization and functional integration, might reveal different effects. Clinical relevance of endpoints: While SWM and s2PD are established measures, a short comment on how observed changes translate into patient-relevant functional outcomes (e.g., dexterity, daily hand use) would further strengthen the clinical interpretation. The use of PROMs could also be discussed. Overall, this is a high-quality study with a clear clinical message. Addressing the points above would further enhance its interpretability and clinical applicability. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: nerve regeneration, nerve surgery, functional recovery I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Heinzel J. Reviewer Report For: Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.5256/f1000research.196634.r474927 ) The direct URL for this report is: https://f1000research.com/articles/14-1222/v2#referee-response-474927 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 29 Apr 2026 Eduardo Silva Reis Barreto , Orthopedics and Traumatology Research Group, Federal University of Bahia (UFBA), Salvador, 40110-100, Brazil 29 Apr 2026 Author Response We thank the reviewer for the positive and constructive assessment of our manuscript. We have revised the Discussion and Study limitations sections to address the main points raised. First, we ... Continue reading We thank the reviewer for the positive and constructive assessment of our manuscript. We have revised the Discussion and Study limitations sections to address the main points raised. First, we expanded the discussion of external validity to clarify that isolated, non-segmental digital nerve injuries represent a relatively favorable sensory nerve injury model. We now state more explicitly that the findings may not be directly generalizable to more clinically challenging scenarios, such as mixed motor-sensory nerve injuries, delayed repairs, segmental defects, nerve gaps, or proximal lesions requiring longer regenerative distances. Second, we added a discussion of dose–response considerations. We now clarify that this trial tested a single 1-hour session of surface PES and therefore cannot exclude the possibility that repeated sessions, different intensities, alternative timing, or longer stimulation schedules could produce different effects. Third, we expanded the discussion of postoperative rehabilitation. We emphasize that structured sensory re-education and hand therapy were ethically appropriate and clinically necessary, but may have promoted recovery in both groups and thereby reduced the ability to detect subtle additive effects of PES. Fourth, we added a limitation regarding the 3-month follow-up. We now state that this period primarily captures early sensory recovery after short-distance digital nerve repair and that later assessments at 6 to 12 months may better reflect sensory refinement, cortical reorganization, functional integration, and patient adaptation during daily hand use. Regarding the clinical relevance of the endpoints, we agree with the reviewer’s point. This issue is now addressed in the revised Discussion together with the related concern raised by Reviewer 1 regarding the sensitivity of SWM and s2PD. We clarify that although SWM and s2PD are established and clinically meaningful tools after digital nerve repair, they may not fully capture subtle treatment-related differences or broader patient-relevant functional outcomes. We also note that CSS and PDI provided patient-reported information on cold sensitivity and pain-related disability, although broader hand-specific PROMs and dexterity-based or daily hand-use assessments may be useful in future studies. Accordingly, the null findings should be interpreted as the absence of a detectable clinical advantage of this protocol, rather than definitive evidence of no biological effect. We thank the reviewer for the positive and constructive assessment of our manuscript. We have revised the Discussion and Study limitations sections to address the main points raised. First, we expanded the discussion of external validity to clarify that isolated, non-segmental digital nerve injuries represent a relatively favorable sensory nerve injury model. We now state more explicitly that the findings may not be directly generalizable to more clinically challenging scenarios, such as mixed motor-sensory nerve injuries, delayed repairs, segmental defects, nerve gaps, or proximal lesions requiring longer regenerative distances. Second, we added a discussion of dose–response considerations. We now clarify that this trial tested a single 1-hour session of surface PES and therefore cannot exclude the possibility that repeated sessions, different intensities, alternative timing, or longer stimulation schedules could produce different effects. Third, we expanded the discussion of postoperative rehabilitation. We emphasize that structured sensory re-education and hand therapy were ethically appropriate and clinically necessary, but may have promoted recovery in both groups and thereby reduced the ability to detect subtle additive effects of PES. Fourth, we added a limitation regarding the 3-month follow-up. We now state that this period primarily captures early sensory recovery after short-distance digital nerve repair and that later assessments at 6 to 12 months may better reflect sensory refinement, cortical reorganization, functional integration, and patient adaptation during daily hand use. Regarding the clinical relevance of the endpoints, we agree with the reviewer’s point. This issue is now addressed in the revised Discussion together with the related concern raised by Reviewer 1 regarding the sensitivity of SWM and s2PD. We clarify that although SWM and s2PD are established and clinically meaningful tools after digital nerve repair, they may not fully capture subtle treatment-related differences or broader patient-relevant functional outcomes. We also note that CSS and PDI provided patient-reported information on cold sensitivity and pain-related disability, although broader hand-specific PROMs and dexterity-based or daily hand-use assessments may be useful in future studies. Accordingly, the null findings should be interpreted as the absence of a detectable clinical advantage of this protocol, rather than definitive evidence of no biological effect. Competing Interests: None. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 29 Apr 2026 Eduardo Silva Reis Barreto , Orthopedics and Traumatology Research Group, Federal University of Bahia (UFBA), Salvador, 40110-100, Brazil 29 Apr 2026 Author Response We thank the reviewer for the positive and constructive assessment of our manuscript. We have revised the Discussion and Study limitations sections to address the main points raised. First, we ... Continue reading We thank the reviewer for the positive and constructive assessment of our manuscript. We have revised the Discussion and Study limitations sections to address the main points raised. First, we expanded the discussion of external validity to clarify that isolated, non-segmental digital nerve injuries represent a relatively favorable sensory nerve injury model. We now state more explicitly that the findings may not be directly generalizable to more clinically challenging scenarios, such as mixed motor-sensory nerve injuries, delayed repairs, segmental defects, nerve gaps, or proximal lesions requiring longer regenerative distances. Second, we added a discussion of dose–response considerations. We now clarify that this trial tested a single 1-hour session of surface PES and therefore cannot exclude the possibility that repeated sessions, different intensities, alternative timing, or longer stimulation schedules could produce different effects. Third, we expanded the discussion of postoperative rehabilitation. We emphasize that structured sensory re-education and hand therapy were ethically appropriate and clinically necessary, but may have promoted recovery in both groups and thereby reduced the ability to detect subtle additive effects of PES. Fourth, we added a limitation regarding the 3-month follow-up. We now state that this period primarily captures early sensory recovery after short-distance digital nerve repair and that later assessments at 6 to 12 months may better reflect sensory refinement, cortical reorganization, functional integration, and patient adaptation during daily hand use. Regarding the clinical relevance of the endpoints, we agree with the reviewer’s point. This issue is now addressed in the revised Discussion together with the related concern raised by Reviewer 1 regarding the sensitivity of SWM and s2PD. We clarify that although SWM and s2PD are established and clinically meaningful tools after digital nerve repair, they may not fully capture subtle treatment-related differences or broader patient-relevant functional outcomes. We also note that CSS and PDI provided patient-reported information on cold sensitivity and pain-related disability, although broader hand-specific PROMs and dexterity-based or daily hand-use assessments may be useful in future studies. Accordingly, the null findings should be interpreted as the absence of a detectable clinical advantage of this protocol, rather than definitive evidence of no biological effect. We thank the reviewer for the positive and constructive assessment of our manuscript. We have revised the Discussion and Study limitations sections to address the main points raised. First, we expanded the discussion of external validity to clarify that isolated, non-segmental digital nerve injuries represent a relatively favorable sensory nerve injury model. We now state more explicitly that the findings may not be directly generalizable to more clinically challenging scenarios, such as mixed motor-sensory nerve injuries, delayed repairs, segmental defects, nerve gaps, or proximal lesions requiring longer regenerative distances. Second, we added a discussion of dose–response considerations. We now clarify that this trial tested a single 1-hour session of surface PES and therefore cannot exclude the possibility that repeated sessions, different intensities, alternative timing, or longer stimulation schedules could produce different effects. Third, we expanded the discussion of postoperative rehabilitation. We emphasize that structured sensory re-education and hand therapy were ethically appropriate and clinically necessary, but may have promoted recovery in both groups and thereby reduced the ability to detect subtle additive effects of PES. Fourth, we added a limitation regarding the 3-month follow-up. We now state that this period primarily captures early sensory recovery after short-distance digital nerve repair and that later assessments at 6 to 12 months may better reflect sensory refinement, cortical reorganization, functional integration, and patient adaptation during daily hand use. Regarding the clinical relevance of the endpoints, we agree with the reviewer’s point. This issue is now addressed in the revised Discussion together with the related concern raised by Reviewer 1 regarding the sensitivity of SWM and s2PD. We clarify that although SWM and s2PD are established and clinically meaningful tools after digital nerve repair, they may not fully capture subtle treatment-related differences or broader patient-relevant functional outcomes. We also note that CSS and PDI provided patient-reported information on cold sensitivity and pain-related disability, although broader hand-specific PROMs and dexterity-based or daily hand-use assessments may be useful in future studies. Accordingly, the null findings should be interpreted as the absence of a detectable clinical advantage of this protocol, rather than definitive evidence of no biological effect. Competing Interests: None. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Kurukuti NM. Reviewer Report For: Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.5256/f1000research.196634.r466700 ) The direct URL for this report is: https://f1000research.com/articles/14-1222/v2#referee-response-466700 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 03 Apr 2026 Nish Mohith Kurukuti , Northwestern University, Evanston, Illinois, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.196634.r466700 I appreciate the authors’ thorough and thoughtful revisions. The manuscript has improved substantially in terms of theoretical clarity, methodological transparency, and interpretation of null findings. Overall, the manuscript is improved. However, I have a few targeted suggestions that would further ... Continue reading READ ALL I appreciate the authors’ thorough and thoughtful revisions. The manuscript has improved substantially in terms of theoretical clarity, methodological transparency, and interpretation of null findings. Overall, the manuscript is improved. However, I have a few targeted suggestions that would further strengthen the paper. I remain unclear regarding how the stimulation intervention was anatomically targeted across participants. The manuscript states that PES was delivered “at the motor threshold of the median nerve,” while Table 1 indicates injuries across multiple digits, including the ring and little fingers, which may involve digital branches outside the median nerve distribution. It is therefore not clear whether stimulation was standardized to the injured digital nerve branch, or whether a more general median nerve-based stimulation approach was used across all participants. This distinction is important because the biological plausibility of the intervention depends on whether the injured nerve was actually engaged in a comparable manner across subjects. While the authors state that “small effect sizes and overlapping confidence intervals” are shown in Figure 3, numerical values are still not explicitly reported in the text or tables. Null results are best interpreted via precision (CI width) and effect magnitude, not just p-values. Furthermore, readers should not have to visually infer this from plots. I would recommend adding a concise table or sentence reporting mean difference (PES vs sham), 95% CI, Effect size (e.g., Cohen’s d or partial η² for ANOVA) The ceiling effect discussion is now adequate. However, I think going a step further with also addressing the sensitivity of the outcome measures would also be helpful. I suggest discussing the possibility that the current chosen outcome measures may not detect small differences and Implication for interpretation of null results Competing Interests: No competing interests were disclosed. Reviewer Expertise: TENS, sensorimotor control, Sensory perception, Motor control, Motor unit physiology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Kurukuti NM. Reviewer Report For: Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.5256/f1000research.196634.r466700 ) The direct URL for this report is: https://f1000research.com/articles/14-1222/v2#referee-response-466700 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 29 Apr 2026 Eduardo Silva Reis Barreto , Orthopedics and Traumatology Research Group, Federal University of Bahia (UFBA), Salvador, 40110-100, Brazil 29 Apr 2026 Author Response We thank the reviewer for the thoughtful and constructive comments, and for recognizing the improvements made in the revised manuscript. We agree that the anatomical targeting of the stimulation protocol ... Continue reading We thank the reviewer for the thoughtful and constructive comments, and for recognizing the improvements made in the revised manuscript. We agree that the anatomical targeting of the stimulation protocol required further clarification. The Methods section has been revised to specify that electrode placement was individualized according to the injured digit and surgical repair site, with electrodes positioned proximal and distal to the neurorrhaphy along the presumed course of the repaired digital nerve. We also clarified that the median nerve motor threshold was used only as an operational reference to standardize stimulation intensity, not as the anatomical target of stimulation. To avoid overstatement, we now acknowledge that selective and equivalent recruitment of the repaired digital nerve branch across all digits cannot be fully confirmed. We also agree that null findings are better interpreted through the magnitude of between-group differences and precision rather than p-values alone. Accordingly, we revised the Results section to include numerical between-group estimates in the original clinical units. Specifically, we added the unadjusted mean differences and 95% confidence intervals for SWM, s2PD, CSS, and PDI at the 3-month assessment. We chose this format rather than standardized effect sizes because mean differences in grams, millimeters, and questionnaire points are more directly interpretable in a clinical trial context. These estimates did not indicate a clear advantage of PES over sham. Finally, we revised the Discussion and Study limitations sections to address the sensitivity of the outcome measures. We now clarify that, although SWM and s2PD are clinically established tools after digital nerve repair, they may not detect subtle treatment-related differences in axonal regeneration, receptor reinnervation, or sensory processing. We also emphasize that this limitation, together with the possible ceiling effect by three months, should be considered when interpreting the null findings. We thank the reviewer for the thoughtful and constructive comments, and for recognizing the improvements made in the revised manuscript. We agree that the anatomical targeting of the stimulation protocol required further clarification. The Methods section has been revised to specify that electrode placement was individualized according to the injured digit and surgical repair site, with electrodes positioned proximal and distal to the neurorrhaphy along the presumed course of the repaired digital nerve. We also clarified that the median nerve motor threshold was used only as an operational reference to standardize stimulation intensity, not as the anatomical target of stimulation. To avoid overstatement, we now acknowledge that selective and equivalent recruitment of the repaired digital nerve branch across all digits cannot be fully confirmed. We also agree that null findings are better interpreted through the magnitude of between-group differences and precision rather than p-values alone. Accordingly, we revised the Results section to include numerical between-group estimates in the original clinical units. Specifically, we added the unadjusted mean differences and 95% confidence intervals for SWM, s2PD, CSS, and PDI at the 3-month assessment. We chose this format rather than standardized effect sizes because mean differences in grams, millimeters, and questionnaire points are more directly interpretable in a clinical trial context. These estimates did not indicate a clear advantage of PES over sham. Finally, we revised the Discussion and Study limitations sections to address the sensitivity of the outcome measures. We now clarify that, although SWM and s2PD are clinically established tools after digital nerve repair, they may not detect subtle treatment-related differences in axonal regeneration, receptor reinnervation, or sensory processing. We also emphasize that this limitation, together with the possible ceiling effect by three months, should be considered when interpreting the null findings. Competing Interests: None. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 29 Apr 2026 Eduardo Silva Reis Barreto , Orthopedics and Traumatology Research Group, Federal University of Bahia (UFBA), Salvador, 40110-100, Brazil 29 Apr 2026 Author Response We thank the reviewer for the thoughtful and constructive comments, and for recognizing the improvements made in the revised manuscript. We agree that the anatomical targeting of the stimulation protocol ... Continue reading We thank the reviewer for the thoughtful and constructive comments, and for recognizing the improvements made in the revised manuscript. We agree that the anatomical targeting of the stimulation protocol required further clarification. The Methods section has been revised to specify that electrode placement was individualized according to the injured digit and surgical repair site, with electrodes positioned proximal and distal to the neurorrhaphy along the presumed course of the repaired digital nerve. We also clarified that the median nerve motor threshold was used only as an operational reference to standardize stimulation intensity, not as the anatomical target of stimulation. To avoid overstatement, we now acknowledge that selective and equivalent recruitment of the repaired digital nerve branch across all digits cannot be fully confirmed. We also agree that null findings are better interpreted through the magnitude of between-group differences and precision rather than p-values alone. Accordingly, we revised the Results section to include numerical between-group estimates in the original clinical units. Specifically, we added the unadjusted mean differences and 95% confidence intervals for SWM, s2PD, CSS, and PDI at the 3-month assessment. We chose this format rather than standardized effect sizes because mean differences in grams, millimeters, and questionnaire points are more directly interpretable in a clinical trial context. These estimates did not indicate a clear advantage of PES over sham. Finally, we revised the Discussion and Study limitations sections to address the sensitivity of the outcome measures. We now clarify that, although SWM and s2PD are clinically established tools after digital nerve repair, they may not detect subtle treatment-related differences in axonal regeneration, receptor reinnervation, or sensory processing. We also emphasize that this limitation, together with the possible ceiling effect by three months, should be considered when interpreting the null findings. We thank the reviewer for the thoughtful and constructive comments, and for recognizing the improvements made in the revised manuscript. We agree that the anatomical targeting of the stimulation protocol required further clarification. The Methods section has been revised to specify that electrode placement was individualized according to the injured digit and surgical repair site, with electrodes positioned proximal and distal to the neurorrhaphy along the presumed course of the repaired digital nerve. We also clarified that the median nerve motor threshold was used only as an operational reference to standardize stimulation intensity, not as the anatomical target of stimulation. To avoid overstatement, we now acknowledge that selective and equivalent recruitment of the repaired digital nerve branch across all digits cannot be fully confirmed. We also agree that null findings are better interpreted through the magnitude of between-group differences and precision rather than p-values alone. Accordingly, we revised the Results section to include numerical between-group estimates in the original clinical units. Specifically, we added the unadjusted mean differences and 95% confidence intervals for SWM, s2PD, CSS, and PDI at the 3-month assessment. We chose this format rather than standardized effect sizes because mean differences in grams, millimeters, and questionnaire points are more directly interpretable in a clinical trial context. These estimates did not indicate a clear advantage of PES over sham. Finally, we revised the Discussion and Study limitations sections to address the sensitivity of the outcome measures. We now clarify that, although SWM and s2PD are clinically established tools after digital nerve repair, they may not detect subtle treatment-related differences in axonal regeneration, receptor reinnervation, or sensory processing. We also emphasize that this limitation, together with the possible ceiling effect by three months, should be considered when interpreting the null findings. Competing Interests: None. Close Report a concern COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 06 Nov 2025 Views 0 Cite How to cite this report: Kurukuti NM. Reviewer Report For: Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.5256/f1000research.187178.r448494 ) The direct URL for this report is: https://f1000research.com/articles/14-1222/v1#referee-response-448494 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 24 Jan 2026 Nish Mohith Kurukuti , Northwestern University, Evanston, Illinois, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.187178.r448494 This manuscript reports a double-blind randomized controlled trial evaluating whether a single postoperative session of low-frequency transcutaneous peripheral electrical stimulation (PES) improves sensory recovery after digital nerve neurorrhaphy. The topic is clinically relevant and timely, particularly given ongoing interest in ... Continue reading READ ALL This manuscript reports a double-blind randomized controlled trial evaluating whether a single postoperative session of low-frequency transcutaneous peripheral electrical stimulation (PES) improves sensory recovery after digital nerve neurorrhaphy. The topic is clinically relevant and timely, particularly given ongoing interest in non-invasive neuromodulation strategies to enhance peripheral nerve regeneration. The study is carefully conducted, prospectively registered, and transparently reported, and it contributes valuable negative/null findings to a literature that is otherwise skewed toward positive results. However, while the methodological execution is generally sound, the manuscript would benefit from clearer justification of the stimulation paradigm, stronger alignment between hypotheses and outcomes, and more critical interpretation of null effects, particularly in light of biological plausibility, ceiling effects, and protocol design choices. Several issues related to statistical reporting, outcome sensitivity, and figure/table presentation should be addressed to improve clarity and scientific impact. Overall, I believe the study is suitable for indexing after moderate revisions. Major Comments: 1. Rationale and biological plausibility of the stimulation protocol The manuscript would benefit from a more explicit justification for the choice of a single 1-hour PES session, particularly when many preclinical and clinical studies suggesting benefit have used either direct nerve stimulation, repeated sessions, or different timing relative to injury and repair. While the authors cite prior work using single-session stimulation, the mechanistic assumptions underlying transcutaneous stimulation at motor threshold—especially in a purely sensory digital nerve—are not sufficiently discussed. The Discussion should more clearly distinguish failure of PES as a modality from failure of the specific PES protocol tested. 2. Sensitivity and ceiling effects of outcome measures The use of SWM and s2PD testing is clinically standard; however, in isolated digital nerve injuries with short regeneration distances, these measures may lack sensitivity to detect incremental benefits. By 3 months, both groups approach near-normal sensory thresholds, suggesting a ceiling effect. Secondary outcomes (CSS and PDI) were assessed only at the final time point, limiting their interpretability as recovery trajectories. The authors should more explicitly frame this as a model-limited sensitivity issue, and discuss whether alternative outcomes (e.g., dynamic 2PD, tactile gnosis tasks, neurophysiology, or longer follow-up) might have been more informative. 3. Statistical analysis and reporting clarity Several aspects of the statistical reporting require clarification: The rationale for switching between parametric and non-parametric tests is described, but results are not always clearly tied to specific tests. Confidence intervals are mentioned conceptually but are not consistently reported numerically in the Results or figures. The handling of age as a covariate, and the post hoc removal of an outlier, are described but could be perceived as analytically fragile without clearer justification. Explicitly report effect sizes and confidence intervals for primary outcomes. Clear indication (in text or tables) of which statistical tests were used for each comparison. A brief clarification that sensitivity analyses did not alter the primary conclusions. 4. Interpretation of null results and conclusions The conclusions are appropriately cautious but could be strengthened by a more theory-driven interpretation. The Discussion sometimes implies uncertainty about PES efficacy in general, whereas the data more specifically speak to surface PES in isolated digital nerve repair under standard rehabilitation. The comparison to studies using implanted or intraoperative stimulation should emphasize differences in current density, fiber recruitment, and timing. Refine the Conclusions to explicitly state that the findings apply to this specific clinical context and stimulation paradigm, rather than PES broadly. Minor Comments: Figures and captions: Figure captions should be more standalone and include key take-home messages, particularly for Figure 3. Axis labels and units should be consistently legible and clearly explained without reference to the main text. Terminology consistency: The manuscript alternates between PES, TENS, and surface electrical stimulation. While related, these terms should be clearly defined and used consistently. Secondary outcomes timing: The limitation of assessing CSS and PDI only at 3 months should be stated more prominently earlier in the Results or Methods. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: TENS, sensorimotor control, Sensory perception, Motor control, Motor unit physiology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Kurukuti NM. Reviewer Report For: Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.5256/f1000research.187178.r448494 ) The direct URL for this report is: https://f1000research.com/articles/14-1222/v1#referee-response-448494 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 11 Mar 2026 Eduardo Silva Reis Barreto , Orthopedics and Traumatology Research Group, Federal University of Bahia (UFBA), Salvador, 40110-100, Brazil 11 Mar 2026 Author Response Review report: “Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial”. February 2026 Dear Editor and Reviewers, Thank you for ... Continue reading Review report: “Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial”. February 2026 Dear Editor and Reviewers, Thank you for your valuable feedback, which has greatly improved the quality and clarity of our manuscript. We have made the requested changes and are available for any further revisions. Below are our responses to the reviewers' comments: #Reviewer 1: This manuscript reports a double-blind randomized controlled trial evaluating whether a single postoperative session of low-frequency transcutaneous peripheral electrical stimulation (PES) improves sensory recovery after digital nerve neurorrhaphy. The topic is clinically relevant and timely, particularly given ongoing interest in non-invasive neuromodulation strategies to enhance peripheral nerve regeneration. The study is carefully conducted, prospectively registered, and transparently reported, and it contributes valuable negative/null findings to a literature that is otherwise skewed toward positive results. However, while the methodological execution is generally sound, the manuscript would benefit from clearer justification of the stimulation paradigm, stronger alignment between hypotheses and outcomes, and more critical interpretation of null effects, particularly in light of biological plausibility, ceiling effects, and protocol design choices. Several issues related to statistical reporting, outcome sensitivity, and figure/table presentation should be addressed to improve clarity and scientific impact. Overall, I believe the study is suitable for indexing after moderate revisions. Major Comments: 1. Rationale and biological plausibility of the stimulation protocol The manuscript would benefit from a more explicit justification for the choice of a single 1-hour PES session, particularly when many preclinical and clinical studies suggesting benefit have used either direct nerve stimulation, repeated sessions, or different timing relative to injury and repair While the authors cite prior work using single-session stimulation, the mechanistic assumptions underlying transcutaneous stimulation at motor threshold—especially in a purely sensory digital nerve—are not sufficiently discussed. The Discussion should more clearly distinguish failure of PES as a modality from failure of the specific PES protocol tested. Author response and action taken: We thank the reviewer for this valuable and insightful comment. In response, we revised the final paragraph of the Introduction to more clearly explain the biological rationale behind the specific stimulation protocol used in this study. We clarified why a single early postoperative session of transcutaneous stimulation at motor threshold was selected, how this choice was inspired by prior experimental and clinical evidence using brief stimulation paradigms, and why the applicability of this approach to purely sensory digital nerves remains uncertain. These changes also help distinguish the absence of effect observed in this trial from a general conclusion about electrical stimulation as a therapeutic modality, emphasizing that our findings refer specifically to the protocol tested. 2. Sensitivity and ceiling effects of outcome measures The use of SWM and s2PD testing is clinically standard; however, in isolated digital nerve injuries with short regeneration distances, these measures may lack sensitivity to detect incremental benefits. By 3 months, both groups approach near-normal sensory thresholds, suggesting a ceiling effect. Secondary outcomes (CSS and PDI) were assessed only at the final time point, limiting their interpretability as recovery trajectories. The authors should more explicitly frame this as a model-limited sensitivity issue, and discuss whether alternative outcomes (e.g., dynamic 2PD, tactile gnosis tasks, neurophysiology, or longer follow-up) might have been more informative. Author response and action taken: We thank the reviewer for this thoughtful and constructive comment. In response, we clarified in the Discussion that the use of isolated digital nerve injuries as a clinical model may have limited the sensitivity of the outcome measures, since the short regeneration distance and favorable natural recovery after repair likely produced a ceiling effect by three months, reducing the ability of standard tests such as SWM and s2PD to detect small incremental differences between groups. We also acknowledged that secondary outcomes (CSS and PDI), assessed only at the final time point, do not allow interpretation of recovery trajectories, and we added a brief consideration that alternative assessments and longer follow-up might have provided greater sensitivity to detect subtle effects. 3. Statistical analysis and reporting clarity Several aspects of the statistical reporting require clarification: (1) The rationale for switching between parametric and non-parametric tests is described, but results are not always clearly tied to specific tests. (2) Confidence intervals are mentioned conceptually but are not consistently reported numerically in the Results or figures. (3) The handling of age as a covariate, and the post hoc removal of an outlier, are described but could be perceived as analytically fragile without clearer justification. (4) Explicitly report effect sizes and confidence intervals for primary outcomes. (5) Clear indication (in text or tables) of which statistical tests were used for each comparison. (6) A brief clarification that sensitivity analyses did not alter the primary conclusions. Author response and action taken: We thank the reviewer for these important observations regarding the clarity of the statistical reporting. In response, we revised the Statistical analysis and Results sections to explicitly link each reported result to the corresponding statistical test, clearly indicating where repeated measures ANOVA, non-parametric alternatives, and independent samples tests were applied. We also clarified the rationale for including age as a covariate and reframed the outlier analysis as a planned sensitivity analysis to assess the robustness of the findings, rather than a post hoc adjustment. The Results were edited to explicitly state the absence of group and group–time interaction effects, and to indicate that effect sizes and overlapping confidence intervals for the primary outcomes are presented in Figure 3. Finally, we added a clear statement confirming that the sensitivity analyses did not alter the primary conclusions of the study. 4. Interpretation of null results and conclusions (1) The conclusions are appropriately cautious but could be strengthened by a more theory-driven interpretation. (2) The Discussion sometimes implies uncertainty about PES efficacy in general, whereas the data more specifically speak to surface PES in isolated digital nerve repair under standard rehabilitation. (3) The comparison to studies using implanted or intraoperative stimulation should emphasize differences in current density, fiber recruitment, and timing. (4) Refine the Conclusions to explicitly state that the findings apply to this specific clinical context and stimulation paradigm, rather than PES broadly. Author response and action taken: We thank the reviewer for this thoughtful and insightful comment. In response, we refined the Discussion to provide a more theory-driven interpretation of the null findings, emphasizing the mechanisms by which electrical stimulation is believed to promote nerve regeneration and clarifying how transcutaneous stimulation at motor threshold in a purely sensory digital nerve may not achieve the current density or selective fiber recruitment described in studies using direct or implanted stimulation. We also expanded the comparison with prior clinical trials to explicitly highlight differences in stimulation delivery, timing, and biological plausibility. Finally, we revised the Conclusion to state more precisely that the findings apply to the specific surface PES protocol tested in this clinical context, rather than to electrical stimulation as a therapeutic modality in general. Minor Comments: Figures and captions: Figure captions should be more standalone and include key take-home messages, particularly for Figure 3. Axis labels and units should be consistently legible and clearly explained without reference to the main text. Author response and action taken: We thank the reviewer for this helpful suggestion. In response, we revised the caption of Figure 3 to make it more self-contained and informative, including explicit descriptions of the variables, units of measurement, and the main findings illustrated in the figure. We also reviewed the axis labels to ensure clarity and consistency, allowing the figure to be interpreted independently from the main text. Terminology consistency: The manuscript alternates between PES, TENS, and surface electrical stimulation. While related, these terms should be clearly defined and used consistently. Author response and action taken: We thank the reviewer for this important observation. We revised the manuscript to ensure consistent terminology throughout the text. The term transcutaneous peripheral electrical stimulation (PES) is now clearly defined at first mention as stimulation delivered through surface electrodes (commonly referred to as TENS), and the abbreviation PES is used consistently thereafter to avoid ambiguity. Secondary outcomes timing: The limitation of assessing CSS and PDI only at 3 months should be stated more prominently earlier in the Results or Methods. Author response and action taken: We thank the reviewer for this helpful suggestion. In response, we clarified in both the Methods and Results sections that CSS and PDI were assessed only at the 3-month follow-up, making this temporal limitation explicit earlier in the manuscript rather than only in the Discussion. Review report: “Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial”. February 2026 Dear Editor and Reviewers, Thank you for your valuable feedback, which has greatly improved the quality and clarity of our manuscript. We have made the requested changes and are available for any further revisions. Below are our responses to the reviewers' comments: #Reviewer 1: This manuscript reports a double-blind randomized controlled trial evaluating whether a single postoperative session of low-frequency transcutaneous peripheral electrical stimulation (PES) improves sensory recovery after digital nerve neurorrhaphy. The topic is clinically relevant and timely, particularly given ongoing interest in non-invasive neuromodulation strategies to enhance peripheral nerve regeneration. The study is carefully conducted, prospectively registered, and transparently reported, and it contributes valuable negative/null findings to a literature that is otherwise skewed toward positive results. However, while the methodological execution is generally sound, the manuscript would benefit from clearer justification of the stimulation paradigm, stronger alignment between hypotheses and outcomes, and more critical interpretation of null effects, particularly in light of biological plausibility, ceiling effects, and protocol design choices. Several issues related to statistical reporting, outcome sensitivity, and figure/table presentation should be addressed to improve clarity and scientific impact. Overall, I believe the study is suitable for indexing after moderate revisions. Major Comments: 1. Rationale and biological plausibility of the stimulation protocol The manuscript would benefit from a more explicit justification for the choice of a single 1-hour PES session, particularly when many preclinical and clinical studies suggesting benefit have used either direct nerve stimulation, repeated sessions, or different timing relative to injury and repair While the authors cite prior work using single-session stimulation, the mechanistic assumptions underlying transcutaneous stimulation at motor threshold—especially in a purely sensory digital nerve—are not sufficiently discussed. The Discussion should more clearly distinguish failure of PES as a modality from failure of the specific PES protocol tested. Author response and action taken: We thank the reviewer for this valuable and insightful comment. In response, we revised the final paragraph of the Introduction to more clearly explain the biological rationale behind the specific stimulation protocol used in this study. We clarified why a single early postoperative session of transcutaneous stimulation at motor threshold was selected, how this choice was inspired by prior experimental and clinical evidence using brief stimulation paradigms, and why the applicability of this approach to purely sensory digital nerves remains uncertain. These changes also help distinguish the absence of effect observed in this trial from a general conclusion about electrical stimulation as a therapeutic modality, emphasizing that our findings refer specifically to the protocol tested. 2. Sensitivity and ceiling effects of outcome measures The use of SWM and s2PD testing is clinically standard; however, in isolated digital nerve injuries with short regeneration distances, these measures may lack sensitivity to detect incremental benefits. By 3 months, both groups approach near-normal sensory thresholds, suggesting a ceiling effect. Secondary outcomes (CSS and PDI) were assessed only at the final time point, limiting their interpretability as recovery trajectories. The authors should more explicitly frame this as a model-limited sensitivity issue, and discuss whether alternative outcomes (e.g., dynamic 2PD, tactile gnosis tasks, neurophysiology, or longer follow-up) might have been more informative. Author response and action taken: We thank the reviewer for this thoughtful and constructive comment. In response, we clarified in the Discussion that the use of isolated digital nerve injuries as a clinical model may have limited the sensitivity of the outcome measures, since the short regeneration distance and favorable natural recovery after repair likely produced a ceiling effect by three months, reducing the ability of standard tests such as SWM and s2PD to detect small incremental differences between groups. We also acknowledged that secondary outcomes (CSS and PDI), assessed only at the final time point, do not allow interpretation of recovery trajectories, and we added a brief consideration that alternative assessments and longer follow-up might have provided greater sensitivity to detect subtle effects. 3. Statistical analysis and reporting clarity Several aspects of the statistical reporting require clarification: (1) The rationale for switching between parametric and non-parametric tests is described, but results are not always clearly tied to specific tests. (2) Confidence intervals are mentioned conceptually but are not consistently reported numerically in the Results or figures. (3) The handling of age as a covariate, and the post hoc removal of an outlier, are described but could be perceived as analytically fragile without clearer justification. (4) Explicitly report effect sizes and confidence intervals for primary outcomes. (5) Clear indication (in text or tables) of which statistical tests were used for each comparison. (6) A brief clarification that sensitivity analyses did not alter the primary conclusions. Author response and action taken: We thank the reviewer for these important observations regarding the clarity of the statistical reporting. In response, we revised the Statistical analysis and Results sections to explicitly link each reported result to the corresponding statistical test, clearly indicating where repeated measures ANOVA, non-parametric alternatives, and independent samples tests were applied. We also clarified the rationale for including age as a covariate and reframed the outlier analysis as a planned sensitivity analysis to assess the robustness of the findings, rather than a post hoc adjustment. The Results were edited to explicitly state the absence of group and group–time interaction effects, and to indicate that effect sizes and overlapping confidence intervals for the primary outcomes are presented in Figure 3. Finally, we added a clear statement confirming that the sensitivity analyses did not alter the primary conclusions of the study. 4. Interpretation of null results and conclusions (1) The conclusions are appropriately cautious but could be strengthened by a more theory-driven interpretation. (2) The Discussion sometimes implies uncertainty about PES efficacy in general, whereas the data more specifically speak to surface PES in isolated digital nerve repair under standard rehabilitation. (3) The comparison to studies using implanted or intraoperative stimulation should emphasize differences in current density, fiber recruitment, and timing. (4) Refine the Conclusions to explicitly state that the findings apply to this specific clinical context and stimulation paradigm, rather than PES broadly. Author response and action taken: We thank the reviewer for this thoughtful and insightful comment. In response, we refined the Discussion to provide a more theory-driven interpretation of the null findings, emphasizing the mechanisms by which electrical stimulation is believed to promote nerve regeneration and clarifying how transcutaneous stimulation at motor threshold in a purely sensory digital nerve may not achieve the current density or selective fiber recruitment described in studies using direct or implanted stimulation. We also expanded the comparison with prior clinical trials to explicitly highlight differences in stimulation delivery, timing, and biological plausibility. Finally, we revised the Conclusion to state more precisely that the findings apply to the specific surface PES protocol tested in this clinical context, rather than to electrical stimulation as a therapeutic modality in general. Minor Comments: Figures and captions: Figure captions should be more standalone and include key take-home messages, particularly for Figure 3. Axis labels and units should be consistently legible and clearly explained without reference to the main text. Author response and action taken: We thank the reviewer for this helpful suggestion. In response, we revised the caption of Figure 3 to make it more self-contained and informative, including explicit descriptions of the variables, units of measurement, and the main findings illustrated in the figure. We also reviewed the axis labels to ensure clarity and consistency, allowing the figure to be interpreted independently from the main text. Terminology consistency: The manuscript alternates between PES, TENS, and surface electrical stimulation. While related, these terms should be clearly defined and used consistently. Author response and action taken: We thank the reviewer for this important observation. We revised the manuscript to ensure consistent terminology throughout the text. The term transcutaneous peripheral electrical stimulation (PES) is now clearly defined at first mention as stimulation delivered through surface electrodes (commonly referred to as TENS), and the abbreviation PES is used consistently thereafter to avoid ambiguity. Secondary outcomes timing: The limitation of assessing CSS and PDI only at 3 months should be stated more prominently earlier in the Results or Methods. Author response and action taken: We thank the reviewer for this helpful suggestion. In response, we clarified in both the Methods and Results sections that CSS and PDI were assessed only at the 3-month follow-up, making this temporal limitation explicit earlier in the manuscript rather than only in the Discussion. Competing Interests: None Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 11 Mar 2026 Eduardo Silva Reis Barreto , Orthopedics and Traumatology Research Group, Federal University of Bahia (UFBA), Salvador, 40110-100, Brazil 11 Mar 2026 Author Response Review report: “Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial”. February 2026 Dear Editor and Reviewers, Thank you for ... Continue reading Review report: “Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial”. February 2026 Dear Editor and Reviewers, Thank you for your valuable feedback, which has greatly improved the quality and clarity of our manuscript. We have made the requested changes and are available for any further revisions. Below are our responses to the reviewers' comments: #Reviewer 1: This manuscript reports a double-blind randomized controlled trial evaluating whether a single postoperative session of low-frequency transcutaneous peripheral electrical stimulation (PES) improves sensory recovery after digital nerve neurorrhaphy. The topic is clinically relevant and timely, particularly given ongoing interest in non-invasive neuromodulation strategies to enhance peripheral nerve regeneration. The study is carefully conducted, prospectively registered, and transparently reported, and it contributes valuable negative/null findings to a literature that is otherwise skewed toward positive results. However, while the methodological execution is generally sound, the manuscript would benefit from clearer justification of the stimulation paradigm, stronger alignment between hypotheses and outcomes, and more critical interpretation of null effects, particularly in light of biological plausibility, ceiling effects, and protocol design choices. Several issues related to statistical reporting, outcome sensitivity, and figure/table presentation should be addressed to improve clarity and scientific impact. Overall, I believe the study is suitable for indexing after moderate revisions. Major Comments: 1. Rationale and biological plausibility of the stimulation protocol The manuscript would benefit from a more explicit justification for the choice of a single 1-hour PES session, particularly when many preclinical and clinical studies suggesting benefit have used either direct nerve stimulation, repeated sessions, or different timing relative to injury and repair While the authors cite prior work using single-session stimulation, the mechanistic assumptions underlying transcutaneous stimulation at motor threshold—especially in a purely sensory digital nerve—are not sufficiently discussed. The Discussion should more clearly distinguish failure of PES as a modality from failure of the specific PES protocol tested. Author response and action taken: We thank the reviewer for this valuable and insightful comment. In response, we revised the final paragraph of the Introduction to more clearly explain the biological rationale behind the specific stimulation protocol used in this study. We clarified why a single early postoperative session of transcutaneous stimulation at motor threshold was selected, how this choice was inspired by prior experimental and clinical evidence using brief stimulation paradigms, and why the applicability of this approach to purely sensory digital nerves remains uncertain. These changes also help distinguish the absence of effect observed in this trial from a general conclusion about electrical stimulation as a therapeutic modality, emphasizing that our findings refer specifically to the protocol tested. 2. Sensitivity and ceiling effects of outcome measures The use of SWM and s2PD testing is clinically standard; however, in isolated digital nerve injuries with short regeneration distances, these measures may lack sensitivity to detect incremental benefits. By 3 months, both groups approach near-normal sensory thresholds, suggesting a ceiling effect. Secondary outcomes (CSS and PDI) were assessed only at the final time point, limiting their interpretability as recovery trajectories. The authors should more explicitly frame this as a model-limited sensitivity issue, and discuss whether alternative outcomes (e.g., dynamic 2PD, tactile gnosis tasks, neurophysiology, or longer follow-up) might have been more informative. Author response and action taken: We thank the reviewer for this thoughtful and constructive comment. In response, we clarified in the Discussion that the use of isolated digital nerve injuries as a clinical model may have limited the sensitivity of the outcome measures, since the short regeneration distance and favorable natural recovery after repair likely produced a ceiling effect by three months, reducing the ability of standard tests such as SWM and s2PD to detect small incremental differences between groups. We also acknowledged that secondary outcomes (CSS and PDI), assessed only at the final time point, do not allow interpretation of recovery trajectories, and we added a brief consideration that alternative assessments and longer follow-up might have provided greater sensitivity to detect subtle effects. 3. Statistical analysis and reporting clarity Several aspects of the statistical reporting require clarification: (1) The rationale for switching between parametric and non-parametric tests is described, but results are not always clearly tied to specific tests. (2) Confidence intervals are mentioned conceptually but are not consistently reported numerically in the Results or figures. (3) The handling of age as a covariate, and the post hoc removal of an outlier, are described but could be perceived as analytically fragile without clearer justification. (4) Explicitly report effect sizes and confidence intervals for primary outcomes. (5) Clear indication (in text or tables) of which statistical tests were used for each comparison. (6) A brief clarification that sensitivity analyses did not alter the primary conclusions. Author response and action taken: We thank the reviewer for these important observations regarding the clarity of the statistical reporting. In response, we revised the Statistical analysis and Results sections to explicitly link each reported result to the corresponding statistical test, clearly indicating where repeated measures ANOVA, non-parametric alternatives, and independent samples tests were applied. We also clarified the rationale for including age as a covariate and reframed the outlier analysis as a planned sensitivity analysis to assess the robustness of the findings, rather than a post hoc adjustment. The Results were edited to explicitly state the absence of group and group–time interaction effects, and to indicate that effect sizes and overlapping confidence intervals for the primary outcomes are presented in Figure 3. Finally, we added a clear statement confirming that the sensitivity analyses did not alter the primary conclusions of the study. 4. Interpretation of null results and conclusions (1) The conclusions are appropriately cautious but could be strengthened by a more theory-driven interpretation. (2) The Discussion sometimes implies uncertainty about PES efficacy in general, whereas the data more specifically speak to surface PES in isolated digital nerve repair under standard rehabilitation. (3) The comparison to studies using implanted or intraoperative stimulation should emphasize differences in current density, fiber recruitment, and timing. (4) Refine the Conclusions to explicitly state that the findings apply to this specific clinical context and stimulation paradigm, rather than PES broadly. Author response and action taken: We thank the reviewer for this thoughtful and insightful comment. In response, we refined the Discussion to provide a more theory-driven interpretation of the null findings, emphasizing the mechanisms by which electrical stimulation is believed to promote nerve regeneration and clarifying how transcutaneous stimulation at motor threshold in a purely sensory digital nerve may not achieve the current density or selective fiber recruitment described in studies using direct or implanted stimulation. We also expanded the comparison with prior clinical trials to explicitly highlight differences in stimulation delivery, timing, and biological plausibility. Finally, we revised the Conclusion to state more precisely that the findings apply to the specific surface PES protocol tested in this clinical context, rather than to electrical stimulation as a therapeutic modality in general. Minor Comments: Figures and captions: Figure captions should be more standalone and include key take-home messages, particularly for Figure 3. Axis labels and units should be consistently legible and clearly explained without reference to the main text. Author response and action taken: We thank the reviewer for this helpful suggestion. In response, we revised the caption of Figure 3 to make it more self-contained and informative, including explicit descriptions of the variables, units of measurement, and the main findings illustrated in the figure. We also reviewed the axis labels to ensure clarity and consistency, allowing the figure to be interpreted independently from the main text. Terminology consistency: The manuscript alternates between PES, TENS, and surface electrical stimulation. While related, these terms should be clearly defined and used consistently. Author response and action taken: We thank the reviewer for this important observation. We revised the manuscript to ensure consistent terminology throughout the text. The term transcutaneous peripheral electrical stimulation (PES) is now clearly defined at first mention as stimulation delivered through surface electrodes (commonly referred to as TENS), and the abbreviation PES is used consistently thereafter to avoid ambiguity. Secondary outcomes timing: The limitation of assessing CSS and PDI only at 3 months should be stated more prominently earlier in the Results or Methods. Author response and action taken: We thank the reviewer for this helpful suggestion. In response, we clarified in both the Methods and Results sections that CSS and PDI were assessed only at the 3-month follow-up, making this temporal limitation explicit earlier in the manuscript rather than only in the Discussion. Review report: “Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial”. February 2026 Dear Editor and Reviewers, Thank you for your valuable feedback, which has greatly improved the quality and clarity of our manuscript. We have made the requested changes and are available for any further revisions. Below are our responses to the reviewers' comments: #Reviewer 1: This manuscript reports a double-blind randomized controlled trial evaluating whether a single postoperative session of low-frequency transcutaneous peripheral electrical stimulation (PES) improves sensory recovery after digital nerve neurorrhaphy. The topic is clinically relevant and timely, particularly given ongoing interest in non-invasive neuromodulation strategies to enhance peripheral nerve regeneration. The study is carefully conducted, prospectively registered, and transparently reported, and it contributes valuable negative/null findings to a literature that is otherwise skewed toward positive results. However, while the methodological execution is generally sound, the manuscript would benefit from clearer justification of the stimulation paradigm, stronger alignment between hypotheses and outcomes, and more critical interpretation of null effects, particularly in light of biological plausibility, ceiling effects, and protocol design choices. Several issues related to statistical reporting, outcome sensitivity, and figure/table presentation should be addressed to improve clarity and scientific impact. Overall, I believe the study is suitable for indexing after moderate revisions. Major Comments: 1. Rationale and biological plausibility of the stimulation protocol The manuscript would benefit from a more explicit justification for the choice of a single 1-hour PES session, particularly when many preclinical and clinical studies suggesting benefit have used either direct nerve stimulation, repeated sessions, or different timing relative to injury and repair While the authors cite prior work using single-session stimulation, the mechanistic assumptions underlying transcutaneous stimulation at motor threshold—especially in a purely sensory digital nerve—are not sufficiently discussed. The Discussion should more clearly distinguish failure of PES as a modality from failure of the specific PES protocol tested. Author response and action taken: We thank the reviewer for this valuable and insightful comment. In response, we revised the final paragraph of the Introduction to more clearly explain the biological rationale behind the specific stimulation protocol used in this study. We clarified why a single early postoperative session of transcutaneous stimulation at motor threshold was selected, how this choice was inspired by prior experimental and clinical evidence using brief stimulation paradigms, and why the applicability of this approach to purely sensory digital nerves remains uncertain. These changes also help distinguish the absence of effect observed in this trial from a general conclusion about electrical stimulation as a therapeutic modality, emphasizing that our findings refer specifically to the protocol tested. 2. Sensitivity and ceiling effects of outcome measures The use of SWM and s2PD testing is clinically standard; however, in isolated digital nerve injuries with short regeneration distances, these measures may lack sensitivity to detect incremental benefits. By 3 months, both groups approach near-normal sensory thresholds, suggesting a ceiling effect. Secondary outcomes (CSS and PDI) were assessed only at the final time point, limiting their interpretability as recovery trajectories. The authors should more explicitly frame this as a model-limited sensitivity issue, and discuss whether alternative outcomes (e.g., dynamic 2PD, tactile gnosis tasks, neurophysiology, or longer follow-up) might have been more informative. Author response and action taken: We thank the reviewer for this thoughtful and constructive comment. In response, we clarified in the Discussion that the use of isolated digital nerve injuries as a clinical model may have limited the sensitivity of the outcome measures, since the short regeneration distance and favorable natural recovery after repair likely produced a ceiling effect by three months, reducing the ability of standard tests such as SWM and s2PD to detect small incremental differences between groups. We also acknowledged that secondary outcomes (CSS and PDI), assessed only at the final time point, do not allow interpretation of recovery trajectories, and we added a brief consideration that alternative assessments and longer follow-up might have provided greater sensitivity to detect subtle effects. 3. Statistical analysis and reporting clarity Several aspects of the statistical reporting require clarification: (1) The rationale for switching between parametric and non-parametric tests is described, but results are not always clearly tied to specific tests. (2) Confidence intervals are mentioned conceptually but are not consistently reported numerically in the Results or figures. (3) The handling of age as a covariate, and the post hoc removal of an outlier, are described but could be perceived as analytically fragile without clearer justification. (4) Explicitly report effect sizes and confidence intervals for primary outcomes. (5) Clear indication (in text or tables) of which statistical tests were used for each comparison. (6) A brief clarification that sensitivity analyses did not alter the primary conclusions. Author response and action taken: We thank the reviewer for these important observations regarding the clarity of the statistical reporting. In response, we revised the Statistical analysis and Results sections to explicitly link each reported result to the corresponding statistical test, clearly indicating where repeated measures ANOVA, non-parametric alternatives, and independent samples tests were applied. We also clarified the rationale for including age as a covariate and reframed the outlier analysis as a planned sensitivity analysis to assess the robustness of the findings, rather than a post hoc adjustment. The Results were edited to explicitly state the absence of group and group–time interaction effects, and to indicate that effect sizes and overlapping confidence intervals for the primary outcomes are presented in Figure 3. Finally, we added a clear statement confirming that the sensitivity analyses did not alter the primary conclusions of the study. 4. Interpretation of null results and conclusions (1) The conclusions are appropriately cautious but could be strengthened by a more theory-driven interpretation. (2) The Discussion sometimes implies uncertainty about PES efficacy in general, whereas the data more specifically speak to surface PES in isolated digital nerve repair under standard rehabilitation. (3) The comparison to studies using implanted or intraoperative stimulation should emphasize differences in current density, fiber recruitment, and timing. (4) Refine the Conclusions to explicitly state that the findings apply to this specific clinical context and stimulation paradigm, rather than PES broadly. Author response and action taken: We thank the reviewer for this thoughtful and insightful comment. In response, we refined the Discussion to provide a more theory-driven interpretation of the null findings, emphasizing the mechanisms by which electrical stimulation is believed to promote nerve regeneration and clarifying how transcutaneous stimulation at motor threshold in a purely sensory digital nerve may not achieve the current density or selective fiber recruitment described in studies using direct or implanted stimulation. We also expanded the comparison with prior clinical trials to explicitly highlight differences in stimulation delivery, timing, and biological plausibility. Finally, we revised the Conclusion to state more precisely that the findings apply to the specific surface PES protocol tested in this clinical context, rather than to electrical stimulation as a therapeutic modality in general. Minor Comments: Figures and captions: Figure captions should be more standalone and include key take-home messages, particularly for Figure 3. Axis labels and units should be consistently legible and clearly explained without reference to the main text. Author response and action taken: We thank the reviewer for this helpful suggestion. In response, we revised the caption of Figure 3 to make it more self-contained and informative, including explicit descriptions of the variables, units of measurement, and the main findings illustrated in the figure. We also reviewed the axis labels to ensure clarity and consistency, allowing the figure to be interpreted independently from the main text. Terminology consistency: The manuscript alternates between PES, TENS, and surface electrical stimulation. While related, these terms should be clearly defined and used consistently. Author response and action taken: We thank the reviewer for this important observation. We revised the manuscript to ensure consistent terminology throughout the text. The term transcutaneous peripheral electrical stimulation (PES) is now clearly defined at first mention as stimulation delivered through surface electrodes (commonly referred to as TENS), and the abbreviation PES is used consistently thereafter to avoid ambiguity. Secondary outcomes timing: The limitation of assessing CSS and PDI only at 3 months should be stated more prominently earlier in the Results or Methods. Author response and action taken: We thank the reviewer for this helpful suggestion. In response, we clarified in both the Methods and Results sections that CSS and PDI were assessed only at the 3-month follow-up, making this temporal limitation explicit earlier in the manuscript rather than only in the Discussion. Competing Interests: None Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 06 Nov 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 3 (revision) 09 May 26 read Version 2 (revision) 11 Mar 26 read read Version 1 06 Nov 25 read Nish Mohith Kurukuti , Northwestern University, Evanston, USA Johannes Heinzel , BG Klinik Tuebingen, University of Tuebingen, Tuebingen, Germany Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Heinzel J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 14 May 2026 | for Version 3 Johannes Heinzel , Department of Hand-, Plastic, Reconstructive and Burn Surgery, BG Klinik Tuebingen, University of Tuebingen, Tuebingen, Baden-Wuerttemberg, Germany 0 Views copyright © 2026 Heinzel J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors have sufficiently addressed my concerns. I endorse publication of this manuscript. Competing Interests No competing interests were disclosed. Reviewer Expertise nerve regeneration, nerve surgery, functional recovery I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Heinzel J. Peer Review Report For: Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.5256/f1000research.200497.r483123) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1222/v3#referee-response-483123 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Heinzel J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 21 Apr 2026 | for Version 2 Johannes Heinzel , Department of Hand-, Plastic, Reconstructive and Burn Surgery, BG Klinik Tuebingen, University of Tuebingen, Tuebingen, Baden-Wuerttemberg, Germany 0 Views copyright © 2026 Heinzel J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This manuscript presents a well-conducted randomized controlled trial addressing a clinically relevant question in peripheral nerve regeneration. The study is methodologically rigorous, clearly reported, and provides valuable negative findings in a field where such data remain underrepresented. I would like to offer several additional comments that may further strengthen the manuscript: External validity and patient selection: The inclusion of isolated, non-segmental digital nerve injuries represents a relatively favorable clinical scenario with inherently good recovery potential. While this is acknowledged, it would be helpful to more explicitly discuss how this limits generalizability to more clinically challenging cases (e.g., mixed nerves, delayed repair, or segmental defects), where adjunctive therapies may be more impactful. Dose–response considerations: The study investigates a single stimulation session. Expanding the discussion to more explicitly address the absence of a dose–response framework would help contextualize the negative findings within the broader neuromodulation literature. Rehabilitation as a potential confounder: All patients underwent structured postoperative physiotherapy, which is appropriate and ethically required. However, given its known impact on sensory recovery, a more explicit discussion of its potential to mask subtle intervention effects would be valuable. Temporal resolution of outcomes: With follow-up limited to 3 months, the study primarily captures early sensory recovery. It would be helpful to briefly discuss whether later time points (e.g., 6–12 months), particularly for cortical reorganization and functional integration, might reveal different effects. Clinical relevance of endpoints: While SWM and s2PD are established measures, a short comment on how observed changes translate into patient-relevant functional outcomes (e.g., dexterity, daily hand use) would further strengthen the clinical interpretation. The use of PROMs could also be discussed. Overall, this is a high-quality study with a clear clinical message. Addressing the points above would further enhance its interpretability and clinical applicability. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise nerve regeneration, nerve surgery, functional recovery I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 29 Apr 2026 Eduardo Silva Reis Barreto, Orthopedics and Traumatology Research Group, Federal University of Bahia (UFBA), Salvador, 40110-100, Brazil We thank the reviewer for the positive and constructive assessment of our manuscript. We have revised the Discussion and Study limitations sections to address the main points raised. First, we expanded the discussion of external validity to clarify that isolated, non-segmental digital nerve injuries represent a relatively favorable sensory nerve injury model. We now state more explicitly that the findings may not be directly generalizable to more clinically challenging scenarios, such as mixed motor-sensory nerve injuries, delayed repairs, segmental defects, nerve gaps, or proximal lesions requiring longer regenerative distances. Second, we added a discussion of dose–response considerations. We now clarify that this trial tested a single 1-hour session of surface PES and therefore cannot exclude the possibility that repeated sessions, different intensities, alternative timing, or longer stimulation schedules could produce different effects. Third, we expanded the discussion of postoperative rehabilitation. We emphasize that structured sensory re-education and hand therapy were ethically appropriate and clinically necessary, but may have promoted recovery in both groups and thereby reduced the ability to detect subtle additive effects of PES. Fourth, we added a limitation regarding the 3-month follow-up. We now state that this period primarily captures early sensory recovery after short-distance digital nerve repair and that later assessments at 6 to 12 months may better reflect sensory refinement, cortical reorganization, functional integration, and patient adaptation during daily hand use. Regarding the clinical relevance of the endpoints, we agree with the reviewer’s point. This issue is now addressed in the revised Discussion together with the related concern raised by Reviewer 1 regarding the sensitivity of SWM and s2PD. We clarify that although SWM and s2PD are established and clinically meaningful tools after digital nerve repair, they may not fully capture subtle treatment-related differences or broader patient-relevant functional outcomes. We also note that CSS and PDI provided patient-reported information on cold sensitivity and pain-related disability, although broader hand-specific PROMs and dexterity-based or daily hand-use assessments may be useful in future studies. Accordingly, the null findings should be interpreted as the absence of a detectable clinical advantage of this protocol, rather than definitive evidence of no biological effect. View more View less Competing Interests None. reply Respond Report a concern Heinzel J. Peer Review Report For: Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.5256/f1000research.196634.r474927) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1222/v2#referee-response-474927 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Kurukuti N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 03 Apr 2026 | for Version 2 Nish Mohith Kurukuti , Northwestern University, Evanston, Illinois, USA 0 Views copyright © 2026 Kurukuti N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I appreciate the authors’ thorough and thoughtful revisions. The manuscript has improved substantially in terms of theoretical clarity, methodological transparency, and interpretation of null findings. Overall, the manuscript is improved. However, I have a few targeted suggestions that would further strengthen the paper. I remain unclear regarding how the stimulation intervention was anatomically targeted across participants. The manuscript states that PES was delivered “at the motor threshold of the median nerve,” while Table 1 indicates injuries across multiple digits, including the ring and little fingers, which may involve digital branches outside the median nerve distribution. It is therefore not clear whether stimulation was standardized to the injured digital nerve branch, or whether a more general median nerve-based stimulation approach was used across all participants. This distinction is important because the biological plausibility of the intervention depends on whether the injured nerve was actually engaged in a comparable manner across subjects. While the authors state that “small effect sizes and overlapping confidence intervals” are shown in Figure 3, numerical values are still not explicitly reported in the text or tables. Null results are best interpreted via precision (CI width) and effect magnitude, not just p-values. Furthermore, readers should not have to visually infer this from plots. I would recommend adding a concise table or sentence reporting mean difference (PES vs sham), 95% CI, Effect size (e.g., Cohen’s d or partial η² for ANOVA) The ceiling effect discussion is now adequate. However, I think going a step further with also addressing the sensitivity of the outcome measures would also be helpful. I suggest discussing the possibility that the current chosen outcome measures may not detect small differences and Implication for interpretation of null results Competing Interests No competing interests were disclosed. Reviewer Expertise TENS, sensorimotor control, Sensory perception, Motor control, Motor unit physiology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 29 Apr 2026 Eduardo Silva Reis Barreto, Orthopedics and Traumatology Research Group, Federal University of Bahia (UFBA), Salvador, 40110-100, Brazil We thank the reviewer for the thoughtful and constructive comments, and for recognizing the improvements made in the revised manuscript. We agree that the anatomical targeting of the stimulation protocol required further clarification. The Methods section has been revised to specify that electrode placement was individualized according to the injured digit and surgical repair site, with electrodes positioned proximal and distal to the neurorrhaphy along the presumed course of the repaired digital nerve. We also clarified that the median nerve motor threshold was used only as an operational reference to standardize stimulation intensity, not as the anatomical target of stimulation. To avoid overstatement, we now acknowledge that selective and equivalent recruitment of the repaired digital nerve branch across all digits cannot be fully confirmed. We also agree that null findings are better interpreted through the magnitude of between-group differences and precision rather than p-values alone. Accordingly, we revised the Results section to include numerical between-group estimates in the original clinical units. Specifically, we added the unadjusted mean differences and 95% confidence intervals for SWM, s2PD, CSS, and PDI at the 3-month assessment. We chose this format rather than standardized effect sizes because mean differences in grams, millimeters, and questionnaire points are more directly interpretable in a clinical trial context. These estimates did not indicate a clear advantage of PES over sham. Finally, we revised the Discussion and Study limitations sections to address the sensitivity of the outcome measures. We now clarify that, although SWM and s2PD are clinically established tools after digital nerve repair, they may not detect subtle treatment-related differences in axonal regeneration, receptor reinnervation, or sensory processing. We also emphasize that this limitation, together with the possible ceiling effect by three months, should be considered when interpreting the null findings. View more View less Competing Interests None. reply Respond Report a concern Kurukuti NM. Peer Review Report For: Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.5256/f1000research.196634.r466700) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1222/v2#referee-response-466700 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Kurukuti N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 24 Jan 2026 | for Version 1 Nish Mohith Kurukuti , Northwestern University, Evanston, Illinois, USA 0 Views copyright © 2026 Kurukuti N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This manuscript reports a double-blind randomized controlled trial evaluating whether a single postoperative session of low-frequency transcutaneous peripheral electrical stimulation (PES) improves sensory recovery after digital nerve neurorrhaphy. The topic is clinically relevant and timely, particularly given ongoing interest in non-invasive neuromodulation strategies to enhance peripheral nerve regeneration. The study is carefully conducted, prospectively registered, and transparently reported, and it contributes valuable negative/null findings to a literature that is otherwise skewed toward positive results. However, while the methodological execution is generally sound, the manuscript would benefit from clearer justification of the stimulation paradigm, stronger alignment between hypotheses and outcomes, and more critical interpretation of null effects, particularly in light of biological plausibility, ceiling effects, and protocol design choices. Several issues related to statistical reporting, outcome sensitivity, and figure/table presentation should be addressed to improve clarity and scientific impact. Overall, I believe the study is suitable for indexing after moderate revisions. Major Comments: 1. Rationale and biological plausibility of the stimulation protocol The manuscript would benefit from a more explicit justification for the choice of a single 1-hour PES session, particularly when many preclinical and clinical studies suggesting benefit have used either direct nerve stimulation, repeated sessions, or different timing relative to injury and repair. While the authors cite prior work using single-session stimulation, the mechanistic assumptions underlying transcutaneous stimulation at motor threshold—especially in a purely sensory digital nerve—are not sufficiently discussed. The Discussion should more clearly distinguish failure of PES as a modality from failure of the specific PES protocol tested. 2. Sensitivity and ceiling effects of outcome measures The use of SWM and s2PD testing is clinically standard; however, in isolated digital nerve injuries with short regeneration distances, these measures may lack sensitivity to detect incremental benefits. By 3 months, both groups approach near-normal sensory thresholds, suggesting a ceiling effect. Secondary outcomes (CSS and PDI) were assessed only at the final time point, limiting their interpretability as recovery trajectories. The authors should more explicitly frame this as a model-limited sensitivity issue, and discuss whether alternative outcomes (e.g., dynamic 2PD, tactile gnosis tasks, neurophysiology, or longer follow-up) might have been more informative. 3. Statistical analysis and reporting clarity Several aspects of the statistical reporting require clarification: The rationale for switching between parametric and non-parametric tests is described, but results are not always clearly tied to specific tests. Confidence intervals are mentioned conceptually but are not consistently reported numerically in the Results or figures. The handling of age as a covariate, and the post hoc removal of an outlier, are described but could be perceived as analytically fragile without clearer justification. Explicitly report effect sizes and confidence intervals for primary outcomes. Clear indication (in text or tables) of which statistical tests were used for each comparison. A brief clarification that sensitivity analyses did not alter the primary conclusions. 4. Interpretation of null results and conclusions The conclusions are appropriately cautious but could be strengthened by a more theory-driven interpretation. The Discussion sometimes implies uncertainty about PES efficacy in general, whereas the data more specifically speak to surface PES in isolated digital nerve repair under standard rehabilitation. The comparison to studies using implanted or intraoperative stimulation should emphasize differences in current density, fiber recruitment, and timing. Refine the Conclusions to explicitly state that the findings apply to this specific clinical context and stimulation paradigm, rather than PES broadly. Minor Comments: Figures and captions: Figure captions should be more standalone and include key take-home messages, particularly for Figure 3. Axis labels and units should be consistently legible and clearly explained without reference to the main text. Terminology consistency: The manuscript alternates between PES, TENS, and surface electrical stimulation. While related, these terms should be clearly defined and used consistently. Secondary outcomes timing: The limitation of assessing CSS and PDI only at 3 months should be stated more prominently earlier in the Results or Methods. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise TENS, sensorimotor control, Sensory perception, Motor control, Motor unit physiology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 11 Mar 2026 Eduardo Silva Reis Barreto, Orthopedics and Traumatology Research Group, Federal University of Bahia (UFBA), Salvador, 40110-100, Brazil Review report: “Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial”. February 2026 Dear Editor and Reviewers, Thank you for your valuable feedback, which has greatly improved the quality and clarity of our manuscript. We have made the requested changes and are available for any further revisions. Below are our responses to the reviewers' comments: #Reviewer 1: This manuscript reports a double-blind randomized controlled trial evaluating whether a single postoperative session of low-frequency transcutaneous peripheral electrical stimulation (PES) improves sensory recovery after digital nerve neurorrhaphy. The topic is clinically relevant and timely, particularly given ongoing interest in non-invasive neuromodulation strategies to enhance peripheral nerve regeneration. The study is carefully conducted, prospectively registered, and transparently reported, and it contributes valuable negative/null findings to a literature that is otherwise skewed toward positive results. However, while the methodological execution is generally sound, the manuscript would benefit from clearer justification of the stimulation paradigm, stronger alignment between hypotheses and outcomes, and more critical interpretation of null effects, particularly in light of biological plausibility, ceiling effects, and protocol design choices. Several issues related to statistical reporting, outcome sensitivity, and figure/table presentation should be addressed to improve clarity and scientific impact. Overall, I believe the study is suitable for indexing after moderate revisions. Major Comments: 1. Rationale and biological plausibility of the stimulation protocol The manuscript would benefit from a more explicit justification for the choice of a single 1-hour PES session, particularly when many preclinical and clinical studies suggesting benefit have used either direct nerve stimulation, repeated sessions, or different timing relative to injury and repair While the authors cite prior work using single-session stimulation, the mechanistic assumptions underlying transcutaneous stimulation at motor threshold—especially in a purely sensory digital nerve—are not sufficiently discussed. The Discussion should more clearly distinguish failure of PES as a modality from failure of the specific PES protocol tested. Author response and action taken: We thank the reviewer for this valuable and insightful comment. In response, we revised the final paragraph of the Introduction to more clearly explain the biological rationale behind the specific stimulation protocol used in this study. We clarified why a single early postoperative session of transcutaneous stimulation at motor threshold was selected, how this choice was inspired by prior experimental and clinical evidence using brief stimulation paradigms, and why the applicability of this approach to purely sensory digital nerves remains uncertain. These changes also help distinguish the absence of effect observed in this trial from a general conclusion about electrical stimulation as a therapeutic modality, emphasizing that our findings refer specifically to the protocol tested. 2. Sensitivity and ceiling effects of outcome measures The use of SWM and s2PD testing is clinically standard; however, in isolated digital nerve injuries with short regeneration distances, these measures may lack sensitivity to detect incremental benefits. By 3 months, both groups approach near-normal sensory thresholds, suggesting a ceiling effect. Secondary outcomes (CSS and PDI) were assessed only at the final time point, limiting their interpretability as recovery trajectories. The authors should more explicitly frame this as a model-limited sensitivity issue, and discuss whether alternative outcomes (e.g., dynamic 2PD, tactile gnosis tasks, neurophysiology, or longer follow-up) might have been more informative. Author response and action taken: We thank the reviewer for this thoughtful and constructive comment. In response, we clarified in the Discussion that the use of isolated digital nerve injuries as a clinical model may have limited the sensitivity of the outcome measures, since the short regeneration distance and favorable natural recovery after repair likely produced a ceiling effect by three months, reducing the ability of standard tests such as SWM and s2PD to detect small incremental differences between groups. We also acknowledged that secondary outcomes (CSS and PDI), assessed only at the final time point, do not allow interpretation of recovery trajectories, and we added a brief consideration that alternative assessments and longer follow-up might have provided greater sensitivity to detect subtle effects. 3. Statistical analysis and reporting clarity Several aspects of the statistical reporting require clarification: (1) The rationale for switching between parametric and non-parametric tests is described, but results are not always clearly tied to specific tests. (2) Confidence intervals are mentioned conceptually but are not consistently reported numerically in the Results or figures. (3) The handling of age as a covariate, and the post hoc removal of an outlier, are described but could be perceived as analytically fragile without clearer justification. (4) Explicitly report effect sizes and confidence intervals for primary outcomes. (5) Clear indication (in text or tables) of which statistical tests were used for each comparison. (6) A brief clarification that sensitivity analyses did not alter the primary conclusions. Author response and action taken: We thank the reviewer for these important observations regarding the clarity of the statistical reporting. In response, we revised the Statistical analysis and Results sections to explicitly link each reported result to the corresponding statistical test, clearly indicating where repeated measures ANOVA, non-parametric alternatives, and independent samples tests were applied. We also clarified the rationale for including age as a covariate and reframed the outlier analysis as a planned sensitivity analysis to assess the robustness of the findings, rather than a post hoc adjustment. The Results were edited to explicitly state the absence of group and group–time interaction effects, and to indicate that effect sizes and overlapping confidence intervals for the primary outcomes are presented in Figure 3. Finally, we added a clear statement confirming that the sensitivity analyses did not alter the primary conclusions of the study. 4. Interpretation of null results and conclusions (1) The conclusions are appropriately cautious but could be strengthened by a more theory-driven interpretation. (2) The Discussion sometimes implies uncertainty about PES efficacy in general, whereas the data more specifically speak to surface PES in isolated digital nerve repair under standard rehabilitation. (3) The comparison to studies using implanted or intraoperative stimulation should emphasize differences in current density, fiber recruitment, and timing. (4) Refine the Conclusions to explicitly state that the findings apply to this specific clinical context and stimulation paradigm, rather than PES broadly. Author response and action taken: We thank the reviewer for this thoughtful and insightful comment. In response, we refined the Discussion to provide a more theory-driven interpretation of the null findings, emphasizing the mechanisms by which electrical stimulation is believed to promote nerve regeneration and clarifying how transcutaneous stimulation at motor threshold in a purely sensory digital nerve may not achieve the current density or selective fiber recruitment described in studies using direct or implanted stimulation. We also expanded the comparison with prior clinical trials to explicitly highlight differences in stimulation delivery, timing, and biological plausibility. Finally, we revised the Conclusion to state more precisely that the findings apply to the specific surface PES protocol tested in this clinical context, rather than to electrical stimulation as a therapeutic modality in general. Minor Comments: Figures and captions: Figure captions should be more standalone and include key take-home messages, particularly for Figure 3. Axis labels and units should be consistently legible and clearly explained without reference to the main text. Author response and action taken: We thank the reviewer for this helpful suggestion. In response, we revised the caption of Figure 3 to make it more self-contained and informative, including explicit descriptions of the variables, units of measurement, and the main findings illustrated in the figure. We also reviewed the axis labels to ensure clarity and consistency, allowing the figure to be interpreted independently from the main text. Terminology consistency: The manuscript alternates between PES, TENS, and surface electrical stimulation. While related, these terms should be clearly defined and used consistently. Author response and action taken: We thank the reviewer for this important observation. We revised the manuscript to ensure consistent terminology throughout the text. The term transcutaneous peripheral electrical stimulation (PES) is now clearly defined at first mention as stimulation delivered through surface electrodes (commonly referred to as TENS), and the abbreviation PES is used consistently thereafter to avoid ambiguity. Secondary outcomes timing: The limitation of assessing CSS and PDI only at 3 months should be stated more prominently earlier in the Results or Methods. Author response and action taken: We thank the reviewer for this helpful suggestion. In response, we clarified in both the Methods and Results sections that CSS and PDI were assessed only at the 3-month follow-up, making this temporal limitation explicit earlier in the manuscript rather than only in the Discussion. View more View less Competing Interests None reply Respond Report a concern Kurukuti NM. Peer Review Report For: Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 3; peer review: 1 approved, 1 approved with reservations] . F1000Research 2026, 14 :1222 ( https://doi.org/10.5256/f1000research.187178.r448494) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1222/v1#referee-response-448494 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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