Efficacy of Transcutaneous Electrical Nerve Stimulation for Post-burn Pruritus

Efficacy of Transcutaneous Electrical Nerve Stimulation for Post-burn Pruritus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy of Transcutaneous Electrical Nerve Stimulation for Post-burn Pruritus Xue Heng, Lei Cao, Ning Li, Jianglin Tan, Gaoxing Luo, Haisheng Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8977907/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background: Itching is a common clinical symptom during wound healing and scar formation. Previous research has demonstrated that transcutaneous electrical nerve stimulation (TENS) can alleviate pain. Nevertheless, evidence regarding the efficacy of TENS for post-burn pruritus remains limited. Methods: We performed a single-center, before-after self-control, retrospective cohort study of burn patients with moderate-to-severe pruritus, treated with TENS,between September 2024 and April 2025.The primary outcome was the 7-day itching improvement rate, defined as a ≥50% reduction in NRS on day 7 compared to baseline. Results: A total of 29 patients with a mean age of 41 ± 10 years and a median TBSA of 17% (IQR: 11–32%) were included. The median scar duration was 78 days (IQR: 55.5-327.5) . Treatment sites were primarily located on the lower extremities (72.41%, 21/29). The 7-day itching improvement rate was 44.83% (13/29) and increased with itch severity. NRS,ISS and 5-D assessments confirmed significant itching improvement at the end of treatment (7 vs 4,8 vs 5,13.5 vs 10.5,P < 0.05).No significant improvement in sleep disturbance,but an enhancement in quality of life was noted (1.5 vs 1,P<0.05). Multivariate logistic regression did not identify significant factors associated with therapeutic efficacy, although the odds ratio for itch severity was the lowest.Patients with extremely severe or severe itching exhibited significantly higher improvement rates than those with moderate itching (100% vs. 45.45% vs. 28.57%, P < 0.05). Conclusion: TENS therapy significantly alleviated pruritus in burn patients, particularly in cases of severe or extremely severe itching. Clinical trial registration and registry URL ChiCTR2500099822, registered at www. medicalresearch.org.cn (Mar 28 ,2025).. Burns Itch Pruritus Transcutaneous electrical nerve stimulation Figures Figure 1 1. Introduction Itching is one of the most prevalent and distressing symptoms following burn injuries. Beyond impairing wound healing and functional recovery, it may lead to sleep disturbances, psychiatric comorbidities, and even suicidal ideation, significantly compromising patients' quality of life [ 1 ]. Studies report itch incidence rates of 93%, 86%, 83%, and 73% in severe adult burn cases at discharge and 6 months, 1 year, and 2 years post-discharge, respectively [ 2 , 3 ]. Currently, antihistamines remain the first-line clinical treatment for post-burn itch. However, their therapeutic efficacy is limited to approximately 20% [ 4 ], likely attributable to the neuropathic dominance in post-burn itch pathogenesis [ 5 ]. Transcutaneous electrical nerve stimulation (TENS), also termed peripheral nerve large-fiber stimulation, is a neuromodulation therapy that delivers specific low-frequency pulsed currents through the skin. It is widely utilized for refractory chronic pain, acute musculoskeletal pain, and physiotherapy. Itch and pain share neurobiological similarities as noxious sensations [ 6 ],and are primarily transmitted via cutaneous Aδ, Aβand C nerve fibers. Therefore, TENS may also alleviate post-burn itching. However, only two clinical studies have investigated the use of TENS for post-burn pruritus. One randomized controlled trial enrolled 20 patients with severe pruritus (VAS ≥ 5), randomly assigning participants to either a TENS group (n = 11) or a standard treatment group (n = 9) [ 7 ]. TENS was administered for one hour per session, once daily over 21 days, using a frequency greater than 180 Hz and a pulse duration below 150 µs. The control group received conventional anti-scar therapy. Results showed a significantly greater reduction in VAS scores in the TENS group compared to the control group (6 ± 2.62 vs. 3 ± 2.62, p < 0.05). A self-controlled clinical trial investigated scrambler therapy in 16 patients with moderate-to-severe pruritus (VAS ≥ 5) [ 8 ]. Treatment consisted of 40-minute daily sessions from Monday to Friday, for a total of ten sessions. Following the final treatment, NRS scores were significantly reduced from baseline (6.75 ± 1.13 vs 4.13 ± 1.45, p < 0.05). These preliminary results indicate that TENS may effectively alleviate post-burn pruritus. In this retrospective cohort study, we included burn patients with moderate-to-severe pruritus—defined as a Numerical Rating Scale (NRS) score ≥ 4—who received TENS therapy, to evaluate its clinical efficacy in managing post-burn itch and explore its potential as a novel treatment approach. 2. Methods 2 .1 Study design and Ethic approval This single-center, retrospective cohort study with a before-after self-control design was conducted at the Institute of Burn Research, Southwest Hospital, Army Medical University from September 2024 to April 2025. The study received approval from the Ethics Committee of Southwest Hospital, Army Medical University (No. KY2025095). In accordance with local regulations, written informed consent was waived. The trial was prospectively registered www.medicalresearch.org.cn (ChiCTR2500099822, Principal investigator: Haisheng Li, Date of registration: Mar 28 ,2025). 2 .2 Study population The study population comprised burn patients who received TENS for moderate-to-severe post-burn itch, identified from the Burn Database of Southwest Hospital. Patients were included if the following criteria were met: 1) Aged 18–60 years; 2) burn patients with moderate-to-severe pruritus, defined as a Numerical Rating Scale (NRS) score ≥4; 3) Received TENS therapy during hospitalization. The exclusion criteria included: 1) Itch secondary to other dermatoses (eczema, dermatitis, allergies, infections) or systemic conditions ( diabetes, long-term dialysis); 2) Incomplete clinical data. 2.3 TENS tre tment Patients routinely underwent an assessment of itching severity one day prior to TENS treatment. Electrodes were positioned on either side of the scar, with the anode placed proximally and the cathode distally. Stimulation parameters were set to a frequency of 100 Hz and a pulse width of 150 μs for 3 seconds, followed by 3 seconds at 2 Hz and 200 μs. The treatment intensity ranged from 15-20mA, optimized to the maximum tolerable intensity without causing muscle contraction. The treatment lasted 30 minutes per session, administered once daily for 7 consecutive days. 2 . 3 Data collection General demographic and clinical data were collected from all patients, including gender, age, body mass index (BMI), total burn surface area (TBSA), burn etiology, TENS treatment site, scar area at the TENS treatment site, itch severity, and duration of scarring at the treatment site. 2 .4 Clinical outcomes The primary outcome was 7-day itching improvement rate.Secondary outcomes included changes of NRS[9],Itch Severity Scale (ISS)[10],Sleep Disturbance- Numerical Rating Scale (SD-NRS), 5-D Pruritus Scale (5-D)[11], Itch Quality of Life Questionnaire (IQOF)[12], and Vancouver Scar Scale (VSS)[13] scores before and after TENS therapy.Multivariate logistic regression analysis was used to identify factors associated with therapeutic efficacy. Pruritus severity was categorized as moderate (NRS 4–6), severe (NRS 7–8), or extremely severe (NRS 9–10).Itch severity of participants were evaluated by NRS at baseline (day 1) up to day 7. Definition of 7-day itching improvement rate：A ≥50% reduction in the NRS score during day 7 of intervention compared to the baseline on randomization. Otherwise, it is considered as no relief.The scales for evaluating itch severity include NRS ,ISS and 5-D. The SD-NRS is employed to assess sleep quality. Quality of life is evaluated using the IQOF scale. The VSS is utilized to measure scar improvement.Pain, ulceration, and infection are considered adverse reactions. 2 . 5 Statistical analysis Data analysis was performed using GraphPad Prism 9 (USA, GraphPad Software Inc.) and SPSS 26.0 (USA, IBM analytics). Descriptive statistics (mean, standard deviation, median, interquartile range [IQR]) were calculated. The Mann-Whitney U test was conducted to compare two medians of categorical variables. Fisher's exact test and chi-square test were applied to assess significant associations between two categorical variables (frequency and percentage). The t test or two-way ANOVA was used to compare two or more means of quantitative variables and Scheffe’s test was performed to compare all two groups as post hoc tests. Multivariate logistic regression (forward LR method, entry: P= 0.05; removal:P=0.10) was used to screen the factors contributing to therapeutic efficacy. Details regarding the variable assignments are shown in Tables S1 .P values<0.05 were considered statistically significant. 3. Results 3 .1 P atient characteristics The study enrolled 29 eligible participants ( Table 1 ), including 26 males (89.66%) and 3 females (10.34%). Participants had a mean age of 41±10 years and a mean BMI of 24.09±3.61 kg/m². Flame burns represented the most common etiology (44.83%, 13/29), followed by scalds (27.59%, 8/29), electrical burns (10.34%, 3/29), and explosion injuries (17.24%, 5/29). The median total burn surface area was 17% TBSA(IQR: 11-32%).The median scar duration was 78 days (IQR: 55.5–327.5), with a median scar area of 1% TBSA (IQR: 0.5–2%). Most of itch occurred on the lower extremities (21/29, 72.41%), while the remaining lesions involved the upper extremities (8/29, 27.59%). 3.2 Primary outcomes The 7-day itching improvement rate was 44.83% (13/29). The baseline itch severity distribution was moderate (NRS 4–6)in 48.28% (14/29), severe (NRS 7–8) in 37.93% (11/29), and extremely severe(NRS 9–10) in 13.79% (4/29) of cases. A 50% or greater reduction in NRS scores over 7 days was achieved by 44.83% (13/29) of participants(7 vs 2). Furthermore, 62.07% (18/29) exhibited more than 30% improvement(7 vs 3), while 17.24% (5/29) experienced symptom reduction exceeding 75%(7 vs 1) ( Table 2 ). 3.3 Secondary outcomes Overall, there was a significant reduction in both NRS , ISS and 5-D scores following TENS treatment of the scars( Table 3 ). The NRS scores remained significantly decreased at day 7 compared to the baseline score (7 vs 4, p < 0.05).Similarly, a significant reduction in the ISS score was observed at the end of treatment (8 vs 5,P < 0.05), manifested by decreased frequency of pruritus, reduced severity of itching, improved discomfort levels, and a smaller affected area.5-D scores also showed a marked reduction (13.5 vs 10.5, p 0.05). No significant reduction was observed in the VSS scores before and after treatment (6 vs 5,P>0.05)( Table 3 ). Quality of life assessments showed that IQOF scores were significantly reduced after TENS therapy (1.5 vs 1,P<0.05). 3.4 Subgroup analysis Multivariate logistic regression was used to identify potential factors associated with therapeutic efficacy. However, the analysis revealed no significant associations between treatment efficacy and gender, age, BMI, scar location, scar area, scar duration, or itch severity( Figure S1 ). Among all the factors, the odds ratio of itch severity was the lowest. Therefore, further subgroup analysis stratified by itch severity was performed. Indeed, The 7-day itching improvement rate increased with itch severity ( Figure 1) . The 7-day itching improvement rate reached 100% in the extremely severe group, which was significantly higher than that in both the moderate (28.57%) and severe (45.45%) groups (P < 0.05). 4. Discussion Itching is a common clinical manifestation during burn wound healing and post-healing scar formation. Itching typically emerges several days after burn and gradually diminishes or resolves over time. However, in some patients, it may persist for years or even lifelong. Reports indicate that the incidence of itching in severely burned adult patients at discharge and at 6 months, 1 year, and 2 years post-discharge is 93%, 86%, 83%, and 73%, respectively [ 2 , 3 ]. Another study reported a pruritus incidence of 37.3% in pediatric patients with smaller burn areas [ 4 ]. Risk factors for post-burn pruritus include deep burn depth, large burn area, multiple surgical interventions, post-traumatic stress disorder, and female sex [ 14 , 15 ]. Beyond impairing wound healing and functional recovery, pruritus may lead to sleep disturbances, psychological disorders, and even suicide, significantly compromising patients' quality of life [ 1 , 16 , 17 ]. Thus, timely and effective alleviation of post-burn pruritus is a critical component of burn management. Current evidence suggests that itching transmission pathways involve pruritogenic substances, itch-selective receptors, afferent nerves, and specific regions of the central nervous system [ 18 , 19 ]. Histamine [ 20 ], a profound pruritogenic mediator, is primarily derived from mast cells, with minor contributions from keratinocytes, sensory neurons, and basophils [ 21 ]. Based on pathophysiological mechanisms, itching is classified into cutaneous (dermatogenic), neuropathic, neurogenic, and psychogenic subtypes. The pathophysiology of post-burn pruritus remains incompletely elucidated. Affected areas often exhibit neuropathic sensory abnormalities such as tingling, electric shock-like sensations, and burning. Consequently, current consensus posits that post-burn pruritus predominantly involves cutaneous and neuropathic mechanisms, with the latter playing a dominant role [ 22 – 25 ]. Antihistamines are currently the first-line clinical treatment for post-burn pruritus, including topical formulations (doxepin cream) [ 26 ] and oral agents (cetirizine, loratadine) [ 27 – 28 ]. However, a study evaluating antihistamine efficacy in burn patients demonstrated only a 20% improvement rate [ 4 ], likely attributable to the neuropathic predominance of post-burn pruritus. While antiepileptics( gabapentin, pregabalin) [ 29 – 32 ] may partially alleviate symptoms, their use is limited by frequent adverse effects such as ataxia and dizziness. Therefore, non-pharmacological interventions for post-burn pruritus are urgently needed. TENS,also termed peripheral nerve large-fiber stimulation, is a neuromodulatory therapy that delivers specific low-frequency pulsed currents through the skin. Since its FDA approval in 1974, TENS has been widely employed for refractory chronic pain, acute musculoskeletal pain, and physiotherapy. By applying low-intensity electrical pulses via conductive gel pads over painful dermatomes, TENS induces multi-mechanistic antinociceptive effects primarily targeting Aβ fibers in peripheral nerves [ 33 – 34 ]. In clinical studies investigating the antinociceptive effects of TENS [ 35 ], the most frequently employed frequencies were 100 Hz for high-frequency stimulation (> 50 Hz) and 2 Hz for low-frequency stimulation ( 50 Hz, typically 100 Hz) stimulation activates large-diameter, non-nociceptive Aβ fibers without engaging small-diameter fibers (C fibers, muscle efferents, or Aδ fibers), producing strong, comfortable, painless sensations.Low-frequency (1–4 Hz, typically 2 Hz) stimulation employs high-intensity pulses that activate motor efferents and small-diameter nociceptive muscle afferents (group III, Aδ, ergoreceptors), eliciting intense, painful pulsations often accompanied by muscle twitching. As pruritus and pain share nociceptive pathways [ 6 ], and cutaneous innervation primarily involves Aβ, Aδ, and C fibers (with Aδ/C fibers mediating both sensations), TENS has shown promise in case reports of refractory chronic itching and post-burn itching [ 6 , 36 ], demonstrating marked symptom relief. Given the limited reports on TENS for burn patients, our team conducted a retrospective analysis of 29 patients with moderate-to-severe post-burn pruritus (NRS ≥ 4) who received TENS therapy. The treatment plan manufacturer-recommended analgesia parameters. Our results showed that TENS therapy significantly alleviated pruritus in burn patients, particularly in cases of severe or extremely severe itching. Furthermore, multiple regression analysis found that the odds ratio of itch severity was the lowest.Although relative small sample size may contribute to no statistical difference of gender, age, BMI, scar location, scar area, or scar duration.This finding is consistent to two clinical trials [ 7 – 8 ]. Results demonstrated significant reductions in NRS, ISS, and 5-D itch scale scores post-treatment, reflecting meaningful itch relief.No significant difference in SD-NRS scores was observed.This might be explained that itching is not the sole contributor to sleep disturbance.VSS scores remained unchanged, consistent with scar maturation being a long-term process beyond the 7-day intervention. Quality of life assessments showed that IQOF scores were significantly reduced after TENS therapy,indicating quality of life improvement.The 7-day itching improvement rate was 44.83% and increased with itch severity. Furthermore, patients who achieved an itch improvement rate exceeding 30% accounted for 62.07% of the total study population.This result far surpasses the efficacy rate observed with oral medications that only a 20% improvement rate[ 4 ]. Subgroup analysis showed enhanced responses in patients with higher itch severity. No adverse events occurred. These findings preliminarily support TENS efficacy for moderate-to-severe post-burn pruritus. To our knowledge, this is one of rare clinical studies assessing the clinical efficacy of TENS for managing post-burn pruritus.However, this study also has some limitations. First, this was a single center,before-after self-control, retrospective study. The possibility of self-resolving pruritus cannot be excluded.Furthermore, some confounding factors such as burn causes could not be excluded due to the nature of retrospective studies. Second, relative small sample size might hide the statistical significance of differences.Third, the results were entirely based on assessments using subjective scales and lacked objective data; however, this approach currently represents the most comprehensive method available for evaluating pruritus.So,large-scale, multicenter, prospective studies are warranted. 5. Conclusions In conclusion, this study demonstrates that TENS effectively alleviates itching in burn patients, with greater efficacy observed in those with more severe symptoms. Declarations Acknowledgements: The authors have no conficting interests with any companies. Authorship contributions: Gaoxing Luo and Haisheng Li conceived and designed the research; Xue Heng and Lei Cao performed the study and acquired the data; Jianglin Tan ,Ning Li, Gaoxing Luo and Haisheng Li analyzed and interpreted the data. All authors were involved in drafting and revising the manuscript and approved the final manuscript. Funding This work was supported by grants from National Natural Science Foundation of China (82002036) and 2024 Clinical Research Incubation Project of Southwest Hospital. The funder had no role in study design, data collection and interpretation, or the decision to submit the manuscript for publication. Data availability statement The data that support the findings of this work are available from the corresponding author on reasonable request. Ethical approval and consent to participate This case series was approved by the Ethics Committee of the First Affiliated Hospital of the Army Military Medical University (No. KY2025095) with waived informed consent.Patient consent was waived due to the retrospective, observational nature of this study. This study was conducted in full compliance with the Declaration of Helsinki (https://www.wma.net/policies-post/wma-declaration-of-helsinki/) for research involving human subjects. Competing interests The authors declare no competing interests. References Chung BY,Kim HB,Jung MJ,et al.Post-burn pruritus[J].Int J Mol Sci,2020,21(11):3880. Nedelec B,LaSalle L.Postburn itch: a review of the literature [J].Wounds,2018,30(1):E118-E124. Goutos,Clarke, Upson, Richardson, P.M. Ghosh, S.J. Review of therapeutic agents for burnspruritus and protocols for management in adult and paediatric patients using the GRADE classificationIndian J. Plast. Surg.2010,43,s51-S62. Vitale M, Fields-Blache C, Luterman A. Severe itching in the patient with burns. J Burn Care Rehabil 1991;12:330–3. Sinha S, Gabriel VA, Arora RK.Interventions for postburn pruritus. Cochrane Database Syst Rev. Anzelc M,Burkhart CG. Pain and pruritus: a study of their similarities and differences[J]. Int J Dermatol, 2020, 59(2):159-164. Whitaker C. The use of TENS for pruritus relief in the burns patient: an individual case report[J/OL]. The Journal of Burn Care & Rehabilitation, 2001, 22(4): 274-276. Hettrick HH, O'Brien K, Laznick H, Sanchez J, Gorga D, Nagler W, Yurt R. Effect of transcutaneous electrical nerve stimulation for the management of burn pruritus: a pilot study. J Burn Care Rehabil. 2004 May-Jun;25(3):236-40. Phan NQ, Blome C, Fritz F, Gerss J, Reich A, Ebata T, et al. Assessment of pruritus intensity: Prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus. Acta Derm Venereol 2012;92:502e7. Beecher SM, Hill R, Kearney L,et al. The pruritus severity scale-a novel tool to assess itch in burns patients[J].Burns Trauma,2021,11(3):156-162 Amtmann D,McMullen K,Kim,et al.Psychometric properties of the modified 5-D itch scale in a burn model system sample of people with burn injury[J]. J Burn Care Res,2017,38(1):e402-e408. Lewis V, Finlay AY. 10 years experience of the Dermatology Life Quality Index (DLQI). J Investig Dermatol Symp Proc 2004;9:169e80. Nedelec B, Correa JA, Rachelska G, Armour A, LaSalle L. Quantitative measurement of hypertrophic scar: intrarater reliability, sensitivity, and speciffcity. J Burn Care Res Publ Am Burn Assoc 2008;29(3):489–500. Zuccaro J,Budd D,Kelly C,et al.Pruritus in the pediatric burn population[J].J Burn Care Res,2022,43(5):1175-1179. Van Loey, N.E.; Bremer, M.; Faber, A.W,; Middelkoop, E.; Nieuwenhuis, M.K. Itching following burns.Epidemiology and predictors.Br 1. Dermatol. 2008, 158, 95-100. Marron, S.E; Tomas-Aragones, L; Boira, S.; (ampos-Rodenas, R. Quality of Life, EmotionalWellbeing andFamily Repercussions in Dermatological Patients Experiencing Chronic Itching: A Pilot Study. Acta Derm.Venereol. 2016,96,331-335. Silverberg, J.l.; Hinami, K.; Trick, wE;, Cella, D. Itch in the General Internal Medicine Setting: ACross-Sectional Study of Prevalence and Quality-of-Life Effects. Am. 1. Clin. Dermatol. 2016, 17, 681-690 Yosipovitch G,Greaves MW,Schmelz M.Itch[J].Lancet,2003, 361(9358): 690-694. Dong X,Dong X.Peripheral and central mechanisms of itch [J].Neuron,2018,98(3):482-494. Papoiu, A.D.; Coghill, R.C.; Kraft, R.A.; Wang, H.; Yosipovitch, G. A tale of two itches. Common featuresand notable differences in brain activation evoked by cowhage and histamine induced itch. Neuroimage 201259,3611-3623. Dalgard FJ, Svensson Å,Halvorsen JA, et al.Itch and mental health in dermatological patients across Europe: a cross-sectional study in 13 countries[J].J Invest Dermatol, 2020,140(3):568-573. Nedelec, B.; LaSalle, L. Post burn Itch: A Review of the Literature. Wounds 2018, 30, E118-E124. Namer, B.; Reeh, P. Scratching an itch. Nat. Neurosci. 2013, 16, 117-118. Steinhoff, M; Schmelz,M; Szabo,L.; Oaklander, A.L. Clinical presentation, management, and pathophysiology of neuropathic itch. Lancet Neurol. 2018,17,709-720. Goutos,I.Neuropathic mechanisms in the pathophysiology of burns pruritus:Redefining directions for therapy and research. Burn Care Res. 2013,34,82-93. Fowler, E.; Yosipovitch,G. Post-Burn Pruritus and Its Management-Current and New Avenues for Treatment.Curr, Trauma Rep.2019,5,90-98. Baker, R.A.; Zeller, R.A.; Klein, R...; Thornton, R.J,; Shuber, J.H.; Marshall, R.E.; Leibfarth, A.G.; Latko, J.A Burn wound itch control using H1 and H2 antagonists. . Burn Care Rehabil. 2001, 22,263-268. Tager, K.; fenkins, M.; Savlors, R.; Warden, G. The Use of Claritin to Control ltching in Thermally Injured Patients. Burn Care Rehabil. 1998,19,S261-S261. Mendham, j.E. Gabapentin for the treatment of itching produced by burns and wound healing in children: pilot study. Burns 2004, 30,851-853. Ahuija, R.B.; Gupta, R.; Gupta, G.; Shrivastava, P. A comparative analysis of cetirizine, gabapentin and theicombination in the relief of post-burn pruritus. Burns 2011, 37, 203-207. Gray, P; Kirby, J.; Smith, M.T,; Cabot, Pj; Williams, B.; Doecke, j; Cramond, T. Pregabalin in severe burn injury pain: A double-blind, randomised placebo-controlled trial. Pain 2011, 152,1279-1288. Ahuja, R.B.; Gupta, G.K. A four arm, double blind, randomized and placebo controlled study of pregabalin in the management of post-burn pruritus.BurHs2013.39 24-29 Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965;150:971-979.. Jones I, Johnson MI. Transcutaneous electrical nerve stimulation. Contin Educ Anaesth Crit Care Pain 2009;9:130-135. Han S, Park KS, Lee H, Kim E, Zhu X, Lee JM, Suh HS. Transcutaneous electrical nerve stimulation (TENS) for pain control in women with primary dysmenorrhoea. Cochrane Database Syst Rev. 2024 Jul 22;7(7):CD013331. Monk B E. Transcutaneous electronic nerve stimulation in the treatment of generalized pruritus[J/OL]. Clinical and Experimental Dermatology, 1993, 18(1): 67-68. Tables Table 1 Patient demographics and characteristics. Categories Total (n=29) Age(Mean±SD) 41.90±10.93 Sex Male, n(%) 26(89.66%) Female, n(%) 3(10.34%) BMI(Mean±SD) 24.09±3.61 Burn etiology Flame burns, n(%) 13(44.83%) Scalds, n(%) 8(27.59%) Explosion, n(%) 5(17.24%) Electric burns, n(%) 3(10.34%) Total burn area (Median, IQR) 17（11,32） Scar area (Median, IQR) 1（0.5,2） Duration of scar (Median, IQR) 78（55.5,327.5） Treatment sites lower , n(%) 21(72.41%) upper, n(%) 8(27.59%) Itch severity moderate, n(%) 14(48.28%) severe , n(%) 11(37.93%) extremely severe, n(%) 4(13.79%) SD=standard deviation, IQR=interquartile range. Table 2 7-Day itching improvement rate in burn patients after TENS treatment 7-day itching improvement rate ≥30%,n(%) ≥50%,n(%) ≥75%,n(%) Total (n=29) 62.07（18/29） 44.83（13/29） 17.24（5/29） Table 3 Changes in burn patients with itch before and after TENS treatment Initial score Final score Z p value NRS (Median, IQR) 7(5,8) 4(2.5,5) -5.209 0.000 ISS (Median, IQR) 8(7,10) 5(5,6) -4.941 0.000 Duration 1(1,1) 1(1,1) -1.952 0.051 S everity 1(1,2) 1(1,1) -2.685 0.007 F requency 1(1,1.5) 1(1,1) -2.458 0.014 D iscomfort 2(2,3) 1(1,2) -4.822 0.000 Area 2(1,3) 1(1,2) -2.848 0.004 SD-NRS (Median, IQR) 3(0,5.5) 0(0,2.75) -1.762 0.078 5-D (Median, IQR) 13.5(11.25,17) 10.5(10,12) -3.258 0.001 IQOF (Median, IQR) 1.5(1,3) 1(1,1.75) -2.502 0.012 VSS (Median, IQR) 6(5,6) 5(4,5.75) -1.457 0.145 IQR=interquartile range. Additional Declarations No competing interests reported. Supplementary Files TableS1.docx FigureS1.jpg Figure S1 Multivariate Logistic regression analysis for therapeutic efficacy CONSORT2025editablechecklist.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 15 Apr, 2026 Reviewers agreed at journal 14 Apr, 2026 Reviewers agreed at journal 13 Apr, 2026 Reviewers invited by journal 13 Mar, 2026 Editor assigned by journal 13 Mar, 2026 Submission checks completed at journal 11 Mar, 2026 First submitted to journal 10 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8977907","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":605774900,"identity":"409e1aa4-4afc-4acc-bdf2-78f80dbee105","order_by":0,"name":"Xue Heng","email":"","orcid":"","institution":"Army Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xue","middleName":"","lastName":"Heng","suffix":""},{"id":605774901,"identity":"59246bee-0ba5-4e5c-929d-53a405d5e17d","order_by":1,"name":"Lei Cao","email":"","orcid":"","institution":"Army Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Cao","suffix":""},{"id":605774902,"identity":"aaa539e1-608e-42d8-b938-7adb922211fa","order_by":2,"name":"Ning Li","email":"","orcid":"","institution":"Army Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ning","middleName":"","lastName":"Li","suffix":""},{"id":605774903,"identity":"a8be4f2b-771b-4f7d-9461-948b8951a97c","order_by":3,"name":"Jianglin Tan","email":"","orcid":"","institution":"Army Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jianglin","middleName":"","lastName":"Tan","suffix":""},{"id":605774904,"identity":"5ecc0561-6810-41bd-91c2-2ba9b58b4498","order_by":4,"name":"Gaoxing Luo","email":"","orcid":"","institution":"Army Medical University","correspondingAuthor":false,"prefix":"","firstName":"Gaoxing","middleName":"","lastName":"Luo","suffix":""},{"id":605774905,"identity":"997da438-40ff-4ea4-8694-022099390660","order_by":5,"name":"Haisheng Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYBACPmYeBoYEhgNAJvMBqFgCfi1sCC1siQ3EaWHgAVEgLTyGRGph5z344cGfO3Lm/Gu+P7qZc5iBnz3HgOHnDnwO40uWSGx7Zmw54+3G5txthxkke94YMPaewesXA4nEhsOJG26chWgxuJFjwMzYhleL8Y+EP4frN9w48xCsxZ4ILWYSCWyHEwzO9zBCbJEgQotFYtthww032Axn525L55E486zgYC8eLfz8Z4xv/vhzWN7g/OEHn3O3WcvxtydvfPATjxYEkEgAU/BoIgLwE6luFIyCUTAKRh4AAKzxVITZkb++AAAAAElFTkSuQmCC","orcid":"","institution":"Army Medical University","correspondingAuthor":true,"prefix":"","firstName":"Haisheng","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2026-02-26 12:38:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8977907/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8977907/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105033811,"identity":"8905c7e4-d188-4b1c-9c84-3d3662f41af6","added_by":"auto","created_at":"2026-03-20 07:21:47","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":47933,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e7-day itching improvement rates in the three groups stratified by itch severity\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8977907/v1/5ac362e59d79c5fd6b825b3f.jpg"},{"id":105036458,"identity":"7544c859-2146-46cf-b870-a97f512ca150","added_by":"auto","created_at":"2026-03-20 07:33:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":931960,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8977907/v1/e56bb882-d723-4298-a731-8f9ab005e1ab.pdf"},{"id":104874934,"identity":"0c783503-418d-46e8-aff0-4837fc6e2995","added_by":"auto","created_at":"2026-03-18 08:34:40","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":18866,"visible":true,"origin":"","legend":"","description":"","filename":"TableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8977907/v1/5699c717920b16b72f4b4ef8.docx"},{"id":104874937,"identity":"8a89725e-3fd5-4516-843b-e34e5b8d2109","added_by":"auto","created_at":"2026-03-18 08:34:40","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":193152,"visible":true,"origin":"","legend":"\u003cp\u003eFigure S1 \u0026nbsp;Multivariate Logistic regression analysis for therapeutic efficacy\u003c/p\u003e","description":"","filename":"FigureS1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8977907/v1/47e640f4171c23dcd8d13577.jpg"},{"id":104874938,"identity":"bcf23494-d845-48c0-b514-483805d40842","added_by":"auto","created_at":"2026-03-18 08:34:40","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":31987,"visible":true,"origin":"","legend":"","description":"","filename":"CONSORT2025editablechecklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-8977907/v1/996a6822d1fd8b85690bfcfc.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of Transcutaneous Electrical Nerve Stimulation for Post-burn Pruritus","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eItching is one of the most prevalent and distressing symptoms following burn injuries. Beyond impairing wound healing and functional recovery, it may lead to sleep disturbances, psychiatric comorbidities, and even suicidal ideation, significantly compromising patients' quality of life [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Studies report itch incidence rates of 93%, 86%, 83%, and 73% in severe adult burn cases at discharge and 6 months, 1 year, and 2 years post-discharge, respectively [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Currently, antihistamines remain the first-line clinical treatment for post-burn itch. However, their therapeutic efficacy is limited to approximately 20% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], likely attributable to the neuropathic dominance in post-burn itch pathogenesis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTranscutaneous electrical nerve stimulation (TENS), also termed peripheral nerve large-fiber stimulation, is a neuromodulation therapy that delivers specific low-frequency pulsed currents through the skin. It is widely utilized for refractory chronic pain, acute musculoskeletal pain, and physiotherapy. Itch and pain share neurobiological similarities as noxious sensations [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e],and are primarily transmitted via cutaneous Aδ, Aβand C nerve fibers. Therefore, TENS may also alleviate post-burn itching. However, only two clinical studies have investigated the use of TENS for post-burn pruritus. One randomized controlled trial enrolled 20 patients with severe pruritus (VAS\u0026thinsp;\u0026ge;\u0026thinsp;5), randomly assigning participants to either a TENS group (n\u0026thinsp;=\u0026thinsp;11) or a standard treatment group (n\u0026thinsp;=\u0026thinsp;9) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. TENS was administered for one hour per session, once daily over 21 days, using a frequency greater than 180 Hz and a pulse duration below 150 \u0026micro;s. The control group received conventional anti-scar therapy. Results showed a significantly greater reduction in VAS scores in the TENS group compared to the control group (6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.62 vs. 3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.62, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). A self-controlled clinical trial investigated scrambler therapy in 16 patients with moderate-to-severe pruritus (VAS\u0026thinsp;\u0026ge;\u0026thinsp;5) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Treatment consisted of 40-minute daily sessions from Monday to Friday, for a total of ten sessions. Following the final treatment, NRS scores were significantly reduced from baseline (6.75\u0026thinsp;\u0026plusmn;\u0026thinsp;1.13 vs 4.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.45, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). These preliminary results indicate that TENS may effectively alleviate post-burn pruritus.\u003c/p\u003e \u003cp\u003eIn this retrospective cohort study, we included burn patients with moderate-to-severe pruritus\u0026mdash;defined as a Numerical Rating Scale (NRS) score\u0026thinsp;\u0026ge;\u0026thinsp;4\u0026mdash;who received TENS therapy, to evaluate its clinical efficacy in managing post-burn itch and explore its potential as a novel treatment approach.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e.1\u003c/strong\u003e \u003cstrong\u003eStudy\u003c/strong\u003e \u003cstrong\u003edesign\u003c/strong\u003e \u003cstrong\u003eand\u003c/strong\u003e \u003cstrong\u003eEthic\u003c/strong\u003e \u003cstrong\u003eapproval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis single-center, retrospective cohort study with a before-after self-control design was conducted at the Institute of Burn Research, Southwest Hospital, Army Medical University from September 2024 to April 2025. The study received approval from the Ethics Committee of Southwest Hospital, Army Medical University (No. KY2025095). In accordance with local regulations, written informed consent was waived. The trial was prospectively registered www.medicalresearch.org.cn (ChiCTR2500099822, Principal investigator: Haisheng Li, Date of registration: \u0026nbsp; \u0026nbsp;Mar 28 ,2025).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e.2\u003c/strong\u003e \u003cstrong\u003eStudy\u003c/strong\u003e \u003cstrong\u003epopulation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study population comprised burn patients who received TENS for moderate-to-severe post-burn itch, identified from the Burn Database of Southwest Hospital. \u0026nbsp;Patients were included if the following criteria were met: 1) Aged 18–60 years; 2) burn patients with moderate-to-severe pruritus,\u0026nbsp;defined as a Numerical Rating Scale (NRS) score\u0026nbsp;≥4; 3) Received TENS therapy during hospitalization. \u0026nbsp;The exclusion criteria included: 1) Itch secondary to other dermatoses (eczema, dermatitis, allergies, infections) or systemic conditions ( diabetes, long-term dialysis); 2) Incomplete clinical data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTENS\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003etre\u003c/strong\u003e\u003cstrong\u003etment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients routinely underwent an assessment of itching severity one day prior to TENS treatment. Electrodes were positioned on either side of the scar, with the anode placed proximally and the cathode distally. Stimulation parameters were set to a frequency of 100 Hz and a pulse width of 150 μs for 3 seconds, followed by 3 seconds at 2 Hz and 200 μs. The treatment intensity ranged from 15-20mA, optimized to the maximum tolerable intensity without causing muscle contraction. The treatment lasted 30 minutes per session, administered once daily for 7 consecutive days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e \u003cstrong\u003eData collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGeneral demographic and clinical data were collected from all patients, including gender, age, body mass index (BMI), total burn surface area (TBSA), burn etiology, TENS treatment site, scar area at the TENS treatment site, itch severity, and duration of scarring at the treatment site.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e.4\u003c/strong\u003e \u003cstrong\u003eClinical\u003c/strong\u003e \u003cstrong\u003eoutcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was 7-day itching improvement rate.Secondary outcomes included changes of NRS[9],Itch Severity Scale (ISS)[10],Sleep Disturbance- Numerical Rating Scale (SD-NRS), 5-D Pruritus Scale (5-D)[11], Itch Quality of Life Questionnaire (IQOF)[12], and Vancouver Scar Scale (VSS)[13] scores \u0026nbsp;before and after TENS therapy.Multivariate logistic regression analysis was used to identify factors associated with therapeutic efficacy. Pruritus severity was categorized as moderate (NRS 4–6), severe (NRS 7–8), or extremely severe (NRS 9–10).Itch severity of participants were evaluated by NRS at baseline (day 1) up to day 7. Definition of 7-day itching improvement rate：A ≥50% reduction in the NRS score during day 7 of intervention compared to the baseline on randomization. Otherwise, it is considered as no relief.The scales for evaluating itch severity include NRS\u0026nbsp;,ISS\u0026nbsp;and 5-D. The SD-NRS is employed to assess sleep quality. Quality of life is evaluated using the IQOF\u0026nbsp;scale. The VSS is utilized to measure scar improvement.Pain, ulceration, and infection are considered adverse reactions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e5\u003c/strong\u003e \u003cstrong\u003eStatistical\u003c/strong\u003e \u003cstrong\u003eanalysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData analysis was performed using GraphPad Prism 9 (USA, GraphPad Software Inc.) and SPSS 26.0 (USA, IBM analytics). Descriptive statistics (mean, standard deviation, median, interquartile range [IQR]) were calculated. The Mann-Whitney U test was conducted to compare two medians of categorical variables. Fisher's exact test and chi-square test were applied to assess significant associations between two categorical variables (frequency and percentage). The t test or two-way ANOVA was used to compare two or more means of quantitative variables and Scheffe’s test was performed to compare all two groups as post hoc tests. Multivariate logistic regression (forward LR method, entry: P= 0.05; removal:P=0.10) was used to screen the factors contributing to\u0026nbsp;therapeutic efficacy. Details regarding the variable assignments are shown in \u003cstrong\u003eTables S1\u003c/strong\u003e.P values\u0026lt;0.05 were considered statistically significant.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003cstrong\u003e.1\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003cstrong\u003eatient characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study enrolled 29 eligible participants (\u003cstrong\u003eTable 1\u003c/strong\u003e), including 26 males (89.66%) and 3 females (10.34%). Participants had a mean age of 41±10 years and a mean BMI of 24.09±3.61 kg/m². Flame burns represented the most common etiology (44.83%, 13/29), followed by scalds (27.59%, 8/29), electrical burns (10.34%, 3/29), and explosion injuries (17.24%, 5/29). The median total burn surface area was 17% TBSA(IQR: 11-32%).The median scar duration was 78 days (IQR: 55.5–327.5), with a median scar area of 1% TBSA (IQR: 0.5–2%). Most of itch occurred on the lower extremities (21/29, 72.41%), while the remaining lesions involved the upper extremities (8/29, 27.59%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePrimary outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe 7-day itching improvement rate was 44.83% (13/29). The baseline itch severity distribution was moderate (NRS 4–6)in 48.28% (14/29), severe (NRS 7–8) in 37.93% (11/29), and extremely severe(NRS 9–10) in 13.79% (4/29) of cases. A 50% or greater reduction in NRS scores over 7 days was achieved by 44.83% (13/29) of participants(7 vs 2). Furthermore, 62.07% (18/29) exhibited more than 30% improvement(7 vs 3), while 17.24% (5/29) experienced symptom reduction exceeding 75%(7 vs 1) (\u003cstrong\u003eTable 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Secondary outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOverall, there was a significant reduction in both NRS , ISS and 5-D scores following TENS treatment of the scars(\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e). The NRS scores remained significantly decreased at day 7 compared to the baseline score (7 vs 4, p \u0026lt; 0.05).Similarly,\u0026nbsp;a\u0026nbsp;significant reduction in the ISS score was observed at the end of treatment (8 vs 5,P \u0026lt; 0.05), manifested by decreased frequency of pruritus, reduced severity of itching, improved discomfort levels, and a smaller affected area.5-D scores also showed a marked reduction (13.5 vs 10.5, p \u0026lt; 0.05)(\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNo statistically significant difference was observed in the SD-NRS scores before and after TENS treatment (P \u0026gt; 0.05). No significant reduction was observed in the VSS scores before and after treatment (6 vs 5,P\u0026gt;0.05)(\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eQuality of life assessments showed that IQOF scores were significantly reduced after TENS therapy (1.5 vs 1,P\u0026lt;0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4\u003c/strong\u003e \u003cstrong\u003eSubgroup\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMultivariate logistic regression was used to identify potential factors associated with therapeutic efficacy. However, the analysis revealed no significant associations between treatment efficacy and gender, age, BMI, scar location, scar area, scar duration, or itch severity(\u003cstrong\u003eFigure S1\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong all the factors, the odds ratio of\u0026nbsp;itch severity was the lowest.\u0026nbsp;Therefore, further subgroup analysis\u0026nbsp;stratified by itch severity\u0026nbsp;was performed. Indeed,\u0026nbsp;The 7-day itching improvement rate increased with itch severity\u0026nbsp;(\u003cstrong\u003eFigure 1)\u003c/strong\u003e. \u0026nbsp;The 7-day itching improvement rate reached 100% in the extremely severe group, which was significantly higher than that in both the moderate (28.57%) and severe (45.45%) groups (P \u0026lt; 0.05).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eItching is a common clinical manifestation during burn wound healing and post-healing scar formation. Itching typically emerges several days after burn and gradually diminishes or resolves over time. However, in some patients, it may persist for years or even lifelong. Reports indicate that the incidence of itching in severely burned adult patients at discharge and at 6 months, 1 year, and 2 years post-discharge is 93%, 86%, 83%, and 73%, respectively [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Another study reported a pruritus incidence of 37.3% in pediatric patients with smaller burn areas [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Risk factors for post-burn pruritus include deep burn depth, large burn area, multiple surgical interventions, post-traumatic stress disorder, and female sex [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Beyond impairing wound healing and functional recovery, pruritus may lead to sleep disturbances, psychological disorders, and even suicide, significantly compromising patients' quality of life [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Thus, timely and effective alleviation of post-burn pruritus is a critical component of burn management.\u003c/p\u003e \u003cp\u003eCurrent evidence suggests that itching transmission pathways involve pruritogenic substances, itch-selective receptors, afferent nerves, and specific regions of the central nervous system [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Histamine [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], a profound pruritogenic mediator, is primarily derived from mast cells, with minor contributions from keratinocytes, sensory neurons, and basophils [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Based on pathophysiological mechanisms, itching is classified into cutaneous (dermatogenic), neuropathic, neurogenic, and psychogenic subtypes. The pathophysiology of post-burn pruritus remains incompletely elucidated. Affected areas often exhibit neuropathic sensory abnormalities such as tingling, electric shock-like sensations, and burning. Consequently, current consensus posits that post-burn pruritus predominantly involves cutaneous and neuropathic mechanisms, with the latter playing a dominant role [\u003cspan additionalcitationids=\"CR23 CR24\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAntihistamines are currently the first-line clinical treatment for post-burn pruritus, including topical formulations (doxepin cream) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] and oral agents (cetirizine, loratadine) [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, a study evaluating antihistamine efficacy in burn patients demonstrated only a 20% improvement rate [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], likely attributable to the neuropathic predominance of post-burn pruritus. While antiepileptics( gabapentin, pregabalin) [\u003cspan additionalcitationids=\"CR30 CR31\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] may partially alleviate symptoms, their use is limited by frequent adverse effects such as ataxia and dizziness. Therefore, non-pharmacological interventions for post-burn pruritus are urgently needed.\u003c/p\u003e \u003cp\u003eTENS,also termed peripheral nerve large-fiber stimulation, is a neuromodulatory therapy that delivers specific low-frequency pulsed currents through the skin. Since its FDA approval in 1974, TENS has been widely employed for refractory chronic pain, acute musculoskeletal pain, and physiotherapy. By applying low-intensity electrical pulses via conductive gel pads over painful dermatomes, TENS induces multi-mechanistic antinociceptive effects primarily targeting Aβ fibers in peripheral nerves [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. In clinical studies investigating the antinociceptive effects of TENS [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], the most frequently employed frequencies were 100 Hz for high-frequency stimulation (\u0026gt;\u0026thinsp;50 Hz) and 2 Hz for low-frequency stimulation (\u0026lt;\u0026thinsp;10 Hz). Frequency is the most critical determinant of TENS efficacy.High-frequency (\u0026gt;\u0026thinsp;50 Hz, typically 100 Hz) stimulation activates large-diameter, non-nociceptive Aβ fibers without engaging small-diameter fibers (C fibers, muscle efferents, or Aδ fibers), producing strong, comfortable, painless sensations.Low-frequency (1\u0026ndash;4 Hz, typically 2 Hz) stimulation employs high-intensity pulses that activate motor efferents and small-diameter nociceptive muscle afferents (group III, Aδ, ergoreceptors), eliciting intense, painful pulsations often accompanied by muscle twitching. As pruritus and pain share nociceptive pathways [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and cutaneous innervation primarily involves Aβ, Aδ, and C fibers (with Aδ/C fibers mediating both sensations), TENS has shown promise in case reports of refractory chronic itching and post-burn itching [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], demonstrating marked symptom relief.\u003c/p\u003e \u003cp\u003eGiven the limited reports on TENS for burn patients, our team conducted a retrospective analysis of 29 patients with moderate-to-severe post-burn pruritus (NRS\u0026thinsp;\u0026ge;\u0026thinsp;4) who received TENS therapy. The treatment plan manufacturer-recommended analgesia parameters. Our results showed that TENS therapy significantly alleviated pruritus in burn patients, particularly in cases of severe or extremely severe itching. Furthermore, multiple regression analysis found that the odds ratio of itch severity was the lowest.Although relative small sample size may contribute to no statistical difference of gender, age, BMI, scar location, scar area, or scar duration.This finding is consistent to two clinical trials [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eResults demonstrated significant reductions in NRS, ISS, and 5-D itch scale scores post-treatment, reflecting meaningful itch relief.No significant difference in SD-NRS scores was observed.This might be explained that itching is not the sole contributor to sleep disturbance.VSS scores remained unchanged, consistent with scar maturation being a long-term process beyond the 7-day intervention. Quality of life assessments showed that IQOF scores were significantly reduced after TENS therapy,indicating quality of life improvement.The 7-day itching improvement rate was 44.83% and increased with itch severity. Furthermore, patients who achieved an itch improvement rate exceeding 30% accounted for 62.07% of the total study population.This result far surpasses the efficacy rate observed with oral medications that only a 20% improvement rate[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Subgroup analysis showed enhanced responses in patients with higher itch severity. No adverse events occurred. These findings preliminarily support TENS efficacy for moderate-to-severe post-burn pruritus.\u003c/p\u003e \u003cp\u003eTo our knowledge, this is one of rare clinical studies assessing the clinical efficacy of TENS for managing post-burn pruritus.However, this study also has some limitations. First, this was a single center,before-after self-control, retrospective study. The possibility of self-resolving pruritus cannot be excluded.Furthermore, some confounding factors such as burn causes could not be excluded due to the nature of retrospective studies. Second, relative small sample size might hide the statistical significance of differences.Third, the results were entirely based on assessments using subjective scales and lacked objective data; however, this approach currently represents the most comprehensive method available for evaluating pruritus.So,large-scale, multicenter, prospective studies are warranted.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eIn conclusion, this study demonstrates that TENS effectively alleviates itching in burn patients, with greater efficacy observed in those with more severe symptoms.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conficting interests with any companies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorship contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGaoxing Luo and \u0026nbsp;Haisheng Li conceived and designed the research; Xue Heng and Lei Cao performed the study and acquired the data; Jianglin Tan ,Ning Li, Gaoxing Luo and \u0026nbsp;Haisheng Li analyzed and interpreted the data. All authors were involved in drafting and revising the manuscript and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from National Natural Science Foundation of China (82002036) and 2024 Clinical Research Incubation Project of Southwest Hospital. The funder had no role in study design, data collection and interpretation, or the decision to submit the manuscript for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this work are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case series was approved by the Ethics Committee of the First Affiliated Hospital of the Army Military Medical University (No. KY2025095) with waived informed consent.Patient consent was waived due to the retrospective, observational nature of this study. This study was conducted in full compliance with the Declaration of Helsinki (https://www.wma.net/policies-post/wma-declaration-of-helsinki/) for research involving human subjects.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChung BY,Kim HB,Jung MJ,et al.Post-burn pruritus[J].Int J Mol Sci,2020,21(11):3880. \u003c/li\u003e\n\u003cli\u003eNedelec B,LaSalle L.Postburn itch: a review of the literature [J].Wounds,2018,30(1):E118-E124.\u003c/li\u003e\n\u003cli\u003eGoutos,Clarke, Upson, Richardson, P.M. Ghosh, S.J. Review of therapeutic agents for burnspruritus and protocols for management in adult and paediatric patients using the GRADE classificationIndian J. Plast. Surg.2010,43,s51-S62. \u003c/li\u003e\n\u003cli\u003eVitale M, Fields-Blache C, Luterman A. Severe itching in the patient with burns. J Burn Care Rehabil 1991;12:330\u0026ndash;3.\u003c/li\u003e\n\u003cli\u003eSinha S, Gabriel VA, Arora RK.Interventions for postburn pruritus. Cochrane Database Syst Rev.\u003c/li\u003e\n\u003cli\u003eAnzelc M,Burkhart CG. Pain and pruritus: a study of their similarities and differences[J]. Int J Dermatol, 2020, 59(2):159-164.\u003c/li\u003e\n\u003cli\u003eWhitaker C. The use of TENS for pruritus relief in the burns patient: an individual case report[J/OL]. The Journal of Burn Care \u0026amp; Rehabilitation, 2001, 22(4): 274-276. \u003c/li\u003e\n\u003cli\u003eHettrick HH, O\u0026apos;Brien K, Laznick H, Sanchez J, Gorga D, Nagler W, Yurt R. Effect of transcutaneous electrical nerve stimulation for the management of burn pruritus: a pilot study. J Burn Care Rehabil. 2004 May-Jun;25(3):236-40. \u003c/li\u003e\n\u003cli\u003ePhan NQ, Blome C, Fritz F, Gerss J, Reich A, Ebata T, et al. Assessment of pruritus intensity: Prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus. Acta Derm Venereol 2012;92:502e7.\u003c/li\u003e\n\u003cli\u003eBeecher SM, Hill R, Kearney L,et al. The pruritus severity scale-a novel tool to assess itch in burns patients[J].Burns Trauma,2021,11(3):156-162\u003c/li\u003e\n\u003cli\u003eAmtmann D,McMullen K,Kim,et al.Psychometric properties of the modified 5-D itch scale in a burn model system sample of people with burn injury[J]. J Burn Care Res,2017,38(1):e402-e408.\u003c/li\u003e\n\u003cli\u003eLewis V, Finlay AY. 10 years experience of the Dermatology Life Quality Index (DLQI). J Investig Dermatol Symp Proc 2004;9:169e80.\u003c/li\u003e\n\u003cli\u003eNedelec B, Correa JA, Rachelska G, Armour A, LaSalle L. Quantitative measurement of hypertrophic scar: intrarater reliability, sensitivity, and speciffcity. J Burn Care Res Publ Am Burn Assoc 2008;29(3):489\u0026ndash;500. \u003c/li\u003e\n\u003cli\u003eZuccaro J,Budd D,Kelly C,et al.Pruritus in the pediatric burn population[J].J Burn Care Res,2022,43(5):1175-1179.\u003c/li\u003e\n\u003cli\u003eVan Loey, N.E.; Bremer, M.; Faber, A.W,; Middelkoop, E.; Nieuwenhuis, M.K. Itching following burns.Epidemiology and predictors.Br 1. Dermatol. 2008, 158, 95-100.\u003c/li\u003e\n\u003cli\u003eMarron, S.E; Tomas-Aragones, L; Boira, S.; (ampos-Rodenas, R. Quality of Life, EmotionalWellbeing andFamily Repercussions in Dermatological Patients Experiencing Chronic Itching: A Pilot Study. Acta Derm.Venereol. 2016,96,331-335.\u003c/li\u003e\n\u003cli\u003eSilverberg, J.l.; Hinami, K.; Trick, wE;, Cella, D. Itch in the General Internal Medicine Setting: ACross-Sectional Study of Prevalence and Quality-of-Life Effects. Am. 1. Clin. Dermatol. 2016, 17, 681-690\u003c/li\u003e\n\u003cli\u003eYosipovitch G,Greaves MW,Schmelz M.Itch[J].Lancet,2003, 361(9358): 690-694. \u003c/li\u003e\n\u003cli\u003eDong X,Dong X.Peripheral and central mechanisms of itch [J].Neuron,2018,98(3):482-494.\u003c/li\u003e\n\u003cli\u003ePapoiu, A.D.; Coghill, R.C.; Kraft, R.A.; Wang, H.; Yosipovitch, G. A tale of two itches. Common featuresand notable differences in brain activation evoked by cowhage and histamine induced itch. Neuroimage 201259,3611-3623.\u003c/li\u003e\n\u003cli\u003eDalgard FJ, Svensson \u0026Aring;,Halvorsen JA, et al.Itch and mental health in dermatological patients across Europe: a cross-sectional study in 13 countries[J].J Invest Dermatol, 2020,140(3):568-573.\u003c/li\u003e\n\u003cli\u003eNedelec, B.; LaSalle, L. Post burn Itch: A Review of the Literature. Wounds 2018, 30, E118-E124. \u003c/li\u003e\n\u003cli\u003eNamer, B.; Reeh, P. Scratching an itch. Nat. Neurosci. 2013, 16, 117-118. \u003c/li\u003e\n\u003cli\u003eSteinhoff, M; Schmelz,M; Szabo,L.; Oaklander, A.L. Clinical presentation, management, and pathophysiology of neuropathic itch. Lancet Neurol. 2018,17,709-720.\u003c/li\u003e\n\u003cli\u003eGoutos,I.Neuropathic mechanisms in the pathophysiology of burns pruritus:Redefining directions for therapy and research. Burn Care Res. 2013,34,82-93. \u003c/li\u003e\n\u003cli\u003eFowler, E.; Yosipovitch,G. Post-Burn Pruritus and Its Management-Current and New Avenues for Treatment.Curr, Trauma Rep.2019,5,90-98.\u003c/li\u003e\n\u003cli\u003eBaker, R.A.; Zeller, R.A.; Klein, R...; Thornton, R.J,; Shuber, J.H.; Marshall, R.E.; Leibfarth, A.G.; Latko, J.A Burn wound itch control using H1 and H2 antagonists. . Burn Care Rehabil. 2001, 22,263-268. \u003c/li\u003e\n\u003cli\u003eTager, K.; fenkins, M.; Savlors, R.; Warden, G. The Use of Claritin to Control ltching in Thermally Injured Patients. Burn Care Rehabil. 1998,19,S261-S261.\u003c/li\u003e\n\u003cli\u003eMendham, j.E. Gabapentin for the treatment of itching produced by burns and wound healing in children: pilot study. Burns 2004, 30,851-853. \u003c/li\u003e\n\u003cli\u003eAhuija, R.B.; Gupta, R.; Gupta, G.; Shrivastava, P. A comparative analysis of cetirizine, gabapentin and theicombination in the relief of post-burn pruritus. Burns 2011, 37, 203-207. \u003c/li\u003e\n\u003cli\u003eGray, P; Kirby, J.; Smith, M.T,; Cabot, Pj; Williams, B.; Doecke, j; Cramond, T. Pregabalin in severe burn injury pain: A double-blind, randomised placebo-controlled trial. Pain 2011, 152,1279-1288.\u003c/li\u003e\n\u003cli\u003eAhuja, R.B.; Gupta, G.K. A four arm, double blind, randomized and placebo controlled study of pregabalin in the management of post-burn pruritus.BurHs2013.39 24-29\u003c/li\u003e\n\u003cli\u003eMelzack R, Wall PD. Pain mechanisms: a new theory. Science 1965;150:971-979..\u003c/li\u003e\n\u003cli\u003eJones I, Johnson MI. Transcutaneous electrical nerve stimulation. Contin Educ Anaesth Crit Care Pain 2009;9:130-135.\u003c/li\u003e\n\u003cli\u003eHan S, Park KS, Lee H, Kim E, Zhu X, Lee JM, Suh HS. Transcutaneous electrical nerve stimulation (TENS) for pain control in women with primary dysmenorrhoea. Cochrane Database Syst Rev. 2024 Jul 22;7(7):CD013331.\u003c/li\u003e\n\u003cli\u003eMonk B E. Transcutaneous electronic nerve stimulation in the treatment of generalized pruritus[J/OL]. Clinical and Experimental Dermatology, 1993, 18(1): 67-68. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1 \u0026nbsp; Patient demographics and characteristics.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"482\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategories\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal (n=29)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge(Mean±SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e41.90±10.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26(89.66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFemale, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3(10.34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI(Mean±SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24.09±3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBurn etiology\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFlame burns, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13(44.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eScalds, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8(27.59%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eExplosion, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5(17.24%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eElectric burns, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3(10.34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal burn area \u0026nbsp; \u0026nbsp; (Median, IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17（11,32）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eScar area (Median, IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1（0.5,2）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of scar (Median, IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e78（55.5,327.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment sites\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003elower , n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e21(72.41%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eupper, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8(27.59%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eItch severity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003emoderate, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14(48.28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;severe , n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11(37.93%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eextremely severe, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4(13.79%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSD=standard deviation, IQR=interquartile range.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e7-Day itching improvement rate\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;in burn patients after\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTENS\u0026nbsp;treatment\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"536\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e7-day itching improvement rate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e≥30%,n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e≥50%,n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e≥75%,n(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTotal (n=29)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e62.07（18/29）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e44.83（13/29）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17.24（5/29）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 \u0026nbsp;Changes in burn patients with itch before and after TENS treatment\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"544\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eInitial score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eFinal score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eZ\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eNRS (Median, IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7(5,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4(2.5,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-5.209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eISS (Median, IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8(7,10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5(5,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-4.941\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDuration\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1(1,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1(1,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-1.952\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eS\u003c/strong\u003e\u003cstrong\u003eeverity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1(1,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1(1,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-2.685\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eF\u003c/strong\u003e\u003cstrong\u003erequency\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1(1,1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1(1,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-2.458\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003cstrong\u003eiscomfort\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2(2,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1(1,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-4.822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eArea\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2(1,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1(1,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-2.848\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSD-NRS (Median, IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3(0,5.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0(0,2.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-1.762\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e5-D (Median, IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13.5(11.25,17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10.5(10,12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-3.258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eIQOF (Median, IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.5(1,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1(1,1.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-2.502\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVSS (Median, IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6(5,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5(4,5.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-1.457\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.145\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIQR=interquartile range.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Burns, Itch, Pruritus, Transcutaneous electrical nerve stimulation","lastPublishedDoi":"10.21203/rs.3.rs-8977907/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8977907/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eItching is a common clinical symptom during wound healing and scar formation. Previous research has demonstrated that transcutaneous electrical nerve stimulation (TENS) can alleviate pain. Nevertheless, evidence regarding the efficacy of TENS for post-burn pruritus remains limited.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe performed a single-center, before-after self-control, retrospective cohort study of burn patients with moderate-to-severe pruritus, treated with TENS,between September 2024 and April 2025.The primary outcome was the 7-day itching improvement rate, defined as a ≥50% reduction in NRS on day 7 compared to baseline.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eA total of 29 patients with a mean age of 41 ± 10 years and a median TBSA of 17% (IQR: 11–32%) were included. The median scar duration was 78 days (IQR: 55.5-327.5) . Treatment sites were primarily located on the lower extremities (72.41%, 21/29). The 7-day itching improvement rate was 44.83% (13/29) and increased with itch severity. NRS,ISS and 5-D assessments confirmed significant itching improvement at the end of treatment (7 vs 4,8 vs 5,13.5 vs 10.5,P \u0026lt; 0.05).No significant improvement in sleep disturbance,but an enhancement in quality of life was noted (1.5 vs 1,P\u0026lt;0.05). Multivariate logistic regression did not identify significant factors associated with therapeutic efficacy, although the odds ratio for itch severity was the lowest.Patients with extremely severe or severe itching exhibited significantly higher improvement rates than those with moderate itching (100% vs. 45.45% vs. 28.57%, P \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eTENS therapy significantly alleviated pruritus in burn patients, particularly in cases of severe or extremely severe itching.\u003c/p\u003e\n\u003cp\u003eClinical trial registration and registry URL ChiCTR2500099822, registered at www. medicalresearch.org.cn (Mar 28 ,2025)..\u003c/p\u003e","manuscriptTitle":"Efficacy of Transcutaneous Electrical Nerve Stimulation for Post-burn Pruritus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-18 08:34:35","doi":"10.21203/rs.3.rs-8977907/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-15T09:26:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"88111300423333138500422926959328495183","date":"2026-04-14T15:03:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"47820942298521344707577743277515990028","date":"2026-04-13T06:10:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-13T10:36:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-13T06:38:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-11T05:42:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Medical Research","date":"2026-03-10T14:12:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f9d6d6d3-9164-49b4-9d19-27974acbe399","owner":[],"postedDate":"March 18th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-18T08:34:35+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-18 08:34:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8977907","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8977907","identity":"rs-8977907","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}