Ultrasound-guided Hydrorelease/Hydrodissection Reduces Gliding Resistance in a Rat Sciatic Nerve Adhesion Model : a preclinical experimental study

Ultrasound-guided Hydrorelease/Hydrodissection Reduces Gliding Resistance in a Rat Sciatic Nerve Adhesion Model : a preclinical experimental study | 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 Ultrasound-guided Hydrorelease/Hydrodissection Reduces Gliding Resistance in a Rat Sciatic Nerve Adhesion Model : a preclinical experimental study Kazuma Miyatake, Shinya Tsujiku, Hyounmin Choe, Yohei Kusaba, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8624003/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Apr, 2026 Read the published version in Journal of Orthopaedic Surgery and Research → Version 1 posted 4 You are reading this latest preprint version Abstract Background Ultrasound-guided nerve hydrodissection (HD), often referred to as hydrorelease (HR) in Asia, is increasingly used for peripheral nerve entrapment. Although HD/HR is clinically applied to separate nerves from surrounding tissues and potentially improve symptoms, its mechanical effects on nerve mobility under perineural adhesions remain incompletely understood. This study aimed to establish a mild rat sciatic nerve adhesion model and to evaluate whether ultrasound-guided HR/HD improves nerve gliding without impairing nerve function. Methods A rat sciatic nerve adhesion model was created in the right thigh by exposing the sciatic nerve, coagulating the nerve bed, and fixing both ends of the nerve to the bed with 8 − 0 nylon sutures; the contralateral side served as control. Adhesion severity was assessed macroscopically at 1, 3, and 6 weeks (stage 0–2) by two examiners, and tensile strength required to detach the nerve from the bed was measured using a digital force gauge. Nerve function at 6 weeks was evaluated by nerve conduction studies (CMAP and motor nerve conduction velocity). Based on model characterization, ultrasound-guided HR/HD was performed at 6 weeks using 2 mL saline to circumferentially dissect the paraneural sheath, and gross adhesion and tensile strength were reassessed one day after injection. Statistical analyses included one-way ANOVA, Tukey’s test, and Kendall’s coefficient of concordance. Results Adhesions progressed over time, with most nerves showing stage 2 adhesions at 6 weeks; inter-observer agreement was high (Kendall’s coefficient 0.92). Tensile strength increased with time (0.91 ± 0.11 N in controls; 1.12 ± 0.29 N at 1 week; 1.72 ± 0.58 N at 3 weeks; 3.10 ± 0.18 N at 6 weeks), with significantly higher values at 3 and 6 weeks compared with earlier time points (P < 0.05). Motor nerve conduction parameters at 6 weeks did not differ significantly between adhesion and control sides. Ultrasound-guided HR/HD significantly reduced tensile strength in the adhesion model (2.05 ± 0.16 N; P < 0.05 vs untreated adhesions), although values remained higher than controls. Conclusions In a rat sciatic nerve adhesion model with preserved nerve conduction, ultrasound-guided HR/HD reduced tensile strength required to detach the nerve from the bed, indicating improved mechanical mobility/gliding under adhesions. These findings support HR/HD as a minimally invasive approach to enhance nerve gliding in mild perineural adhesion conditions and warrant further studies on long-term outcomes and imaging–pathology correlations. Adhesion of Peripheral nerve Nerve hydrodissection (HD) Hydrorelease (HR) Nerve gliding resistance Tensile strength Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Background Peripheral nerve entrapment (for example carpal tunnel syndrome, cubital tunnel syndrome ...etc) is a common condition encountered in daily clinical practice. Treatment options for peripheral nerve entrapment include surgical intervention and pharmacological therapy, with injections serving as a viable alternative. With advancements in ultrasonography, the visualization of peripheral nerves has greatly improved, leading to increased use of nerve hydrodissection (HD) as a treatment for peripheral nerve entrapment. HD involves the injection of a solution, such as an anesthetic or saline, to separate the nerve from surrounding tissues, including fascia or adjacent structures, thereby alleviating entrapment and associated symptoms. 1 In Asia, the term "hydrorelease" (HR) has become widely adopted to describe a similar technique targeting peripheral nerves. While both HD and HR are used to treat nerve entrapment, the precise mechanisms and comparative efficacy of these techniques remain subjects of ongoing investigation. HD has been applied successfully to various nerves, including the median, ulnar, sural, and nerve roots, demonstrating its versatility in clinical practice. 2 – 6 The choice of solution in HD, whether saline, 5% glucose, or other substances, 4 has sparked debate, with some evidence suggesting that the physical separation of tissues plays a key role in pain relief. A cadaveric study from the Mayo Clinic supports this theory, showing that HD reduces the gliding resistance of the median nerve within the carpal tunnel, indicating beneficial mechanical changes in nerve movement. 7 Despite these advancements, the effects of HD on nerve gliding, particularly in cases of nerve adhesions, are not fully understood. To address this gap, we developed a mild adhesion model of the rat sciatic nerve to investigate the potential of HD/HR to improve nerve compromised by adhesions. We hypothesize that HD/HR will enhance the gliding of the sciatic nerve affected by adhesions, offering insights into its therapeutic potential. Methods Experiment 1: Creation of a Rat Sciatic Nerve Adhesion Model We created a rat sciatic nerve adhesion model based on the rabbit model described by Abe et al., choosing rats due to their easier handling.. 8,9 The procedure involved the following steps in the right thigh of each rat (Fig. 1 ), with the left thigh serving as an untreated control. 1. A mixed anesthetic( Medetomidine Hydrochloride: 0.06 mg/mL, Midazolam: 0.8 mg/mL, Butorphanol Tartrate: 1 mg/mL) was administered subcutaneously to anesthetize the rats (2.5 mL/kg). 2. After shaving the right thigh, the surgical area was disinfected with ethanol and povidone-iodine (10% Povidone-Iodine Solution, Yoshida Pharmaceutical Co., Ltd.). 3. An incision was made on the right thigh to expose the sciatic nerve, which was then dissected, and the nerve beds were coagulated using an electrocautery device. 4. Both ends of the sciatic nerve were fixed to the nerve bed using 8 − 0 nylon sutures. 5. The muscles and skin were sutured separately. 6. The sutured area was disinfected with povidone-iodine, and atipamezole hydrochloride solution (2.5 mL) was administered subcutaneously before returning the animals to their cages. Evaluation of the Degree of Adhesion (Gross Evaluation and Biomechanical examination) For the 1-, 3-, and 6-week evaluation groups, the following procedures were conducted: 1 week (n = 6), 3 weeks (n = 6), and 6 weeks (n = 7) after the creation of the nerve adhesion model. The sciatic nerve on the contralateral side (n = 7) served as the control for comparative analysis. Rats were euthanized under isoflurane anesthesia using the arteriovenous transection method. An incision was made in the right thigh to visually inspect the degree of adhesion between the sciatic nerve and the surrounding tissues. Photographs were taken with a digital camera for documentation. Adhesion was evaluated as follows: stage 0, no adhesion; stage 1, a thin film on the nerve surface and mild adhesion observed; and stage 2, scar tissue around the nerve with moderate adhesion observed (Fig. 2 ). Two examiners independently classified the cases, and in instances where their assessments differed, a consensus was reached through discussion. Biomechanical examination was performed following the method described by Ikeda et al. 9 The distal portion of the sciatic nerve and sutures in the right thigh were removed. The sciatic nerve was then tied to a digital force gauge (DST-20N, Imada Co., Ltd.) using a 3 − 0 silk thread. The gauge was placed 5 cm from the nerve, and the sciatic nerve was pulled vertically to measure the tensile strength required to detach it from the nerve bed (Fig. 3 ). Electrophysiological Evaluation Based on the results from the adhesion model, rats (n = 6) were evaluated 6 weeks post-surgery. Sodium secobarbital (Ional-sodium, Nippon Chemiphar Co., Ltd.) at 50 mg/kg was administered intraperitoneally to anesthetize the rats. The lumbar and dorsal areas were shaved, and the animals were placed in a prone position. Stimulation electrodes (needle electrodes, Unique Medical Co., Ltd.) were positioned near the sciatic nerve (for distal stimulation), near the Achilles tendon (for proximal stimulation), and in the plantar muscle (for recording) of each hind limb (right (n = 6), adhesion side; left (n = 6), contralateral side) (Fig. 4 ). Body temperature was maintained within the range of 37–38°C. Rectangular wave stimulation (1 Hz, 0.1 msec, submax voltage) was delivered using an electrical stimulator (SEN-3301 or SEN-3401MG, Nihon Kohden Corporation) to the distal and proximal stimulation electrodes. The elicited potentials were recorded by the recording electrode and input into a polygraph system (RMT-1000, Nihon Kohden Corporation) via a bioelectric amplifier (PB-101H, Nihon Kohden Corporation). Nerve conduction velocity was calculated based on the conduction times from both the distal and proximal sites and the distance between the electrodes. The amplitude of the M-wave was measured using analysis software (LabChart, ADInstruments). This measurement was repeated three times with sufficient rest between each measurement, and the average value was used. Experiment 2: Ultrasound-guided Hydrorelease/Hydrodissection for a Rat Sciatic Nerve Adhesion Model Based on results from Experiment 1, rats (n = 7) were used at 6 weeks post-surgery. Under isoflurane anesthesia (Isoflurane Inhalation Anesthetic 'VTRS,’ Mylan EPD G.K.), HR/HD was performed using ultrasound guidance. An experienced physician utilized a general-purpose ultrasound diagnostic device (Aplio i900; Canon Medical Systems Corporation) to visualize the sciatic nerve in the right thigh. The nerve was displayed in a single-axis image without piercing it. The procedure involved the circumferential dissection of the paraneural sheath around the nerve bed (Fig. 5 ). A total of 2 mL of saline was used as the dissection solution to sufficiently separate the nerve. Evaluation of the Degree of Adhesion (Gross Evaluation and Biomechanical Examination) Gross evaluation and biomechanical examination were conducted a day after injection using the same methods as in Experiment 1. The results were compared to those of Experiment 1. Raw individual-level data and variable definitions are provided as Supplementary Information (Additional files 1–2). Statistical Analysis The results of the distal CMAP, proximal CMAP, and nerve conduction velocity in the non-adhesion and 6-week post-operative adhesion groups were analyzed using one-way analysis of variance (ANOVA). Comparisons of tensile strength among the non-adhesion, 1-week, 3-week, and 6-week post-operative groups were performed using Tukey’s test. Inter-observer agreement for visual adhesion assessment was evaluated using Kendall’s coefficient of concordance. Comparisons between the untreated 6-week adhesion group (Experiment 1) and the adhesion + HR/HD group (Experiment 2) were unpaired because different animals were used in each group. Results Gross Evaluation and Biomechanical Examination (Experiment 1) Of the 26 cases, consensus between the evaluators was achieved in 23 instances, while three cases required further discussion for classification. The Kendall’s coefficient of concordance was 0.92, indicating high agreement between evaluators. All healthy side adhesions (n = 7) were classified as stage 0. At 1 week post-operation, the distribution was as follows: stage 0 (3 cases), stage 1 (2 cases), and stage 2 (1 case). By 3 weeks, the distribution shifted to stage 0 (0 cases), stage 1 (3 cases), and stage 2 (3 cases). At 6 weeks, the majority were classified as stage 2 (5 cases), with the remaining two cases at stage 1, showing a clear progression of adhesion severity over time (Fig. 6 )(Table 1). The biomechanical examination revealed a significant increase in tensile strength over time: 0.91 ± 0.11 N (no adhesion), 1.12 ± 0.29 N (1 week), 1.72 ± 0.58 N (3 weeks), 3.10 ± 0.18 N (6 weeks). Notably, the tensile strength at 3 and 6 weeks was significantly higher than that at earlier stages (P < 0.05). (figure.7) Electrophysiological Evaluation (Experiment 1) The latency in the healthy group was 38.1 ± 1.75 m/sec, compared to 41.7 ± 1.17 m/sec in the adhesion group. Despite the differences in values, no significant difference in latency was observed between the adhesion and healthy groups (Fig. 8 ). Effect of HR/HD on Adhesions (Experiments 1 and 2) In the Adhesion་HR/HD group, post-operative adhesion stages were classified as stage 1 in 3 cases and stage 2 in 4 cases. The tensile strength required to detach the sciatic nerve in the presence of adhesions plus HR/HD treatment was 2.05 ± 0.16 N (n = 7) (Fig. 9 ). Compared to the untreated adhesion group, HR/HD treatment significantly reduced tensile strength (p < 0.05). However, the tensile strength remained slightly higher than in the no-adhesion group, indicating that the treatment did not fully revert the condition to a state of no adhesion. The untreated adhesion group and the adhesion + HR/HD group consisted of different animals. Discussion We successfully developed a model in which adhesions progressively worsened over the post-operative weeks. This model effectively replicates the mild neuropathy often observed in clinical practice, as it induces a mild degree of adhesion while maintaining normal nerve conduction velocity. Furthermore, in the sciatic nerve adhesion model, HR/HD demonstrated a reduction in tensile strength and an improvement in nerve gliding, even in nerves that had developed adhesions. Our model, characterized by a robust adhesion at 6 weeks postoperatively, demonstrates that adhesions increase in severity over time. Adhesion assessment is commonly performed using Petersen's classification, which evaluates wound healing and the actual detachment of the nerve during dissection. In this study, we developed a visual adhesion assessment method with high inter-rater reliability. Future studies should aim to develop models with stronger adhesions and create a more detailed classification system, incorporating histological evaluations to enhance accuracy. In nerve conduction velocity tests, severe adhesions were associated with decreases in CMAP and MCV. However, the variability in adhesion severity can lead to a mixture of normal and abnormal nerve conduction velocities. Our model, which achieved milder adhesions by minimizing ablation of the nerve bed and targeting only the regions in contact with the nerve, successfully maintained normal nerve conduction velocity. This finding contrasts with previous reports and suggests that our model more accurately represents mild neuropathies frequently encountered in clinical practice. Moreover, HR/HD is known to be more effective in treating mild to moderate neuropathies than severe ones. 11 In daily practice, patients often present with nerve-origin pain without abnormalities in imaging or nerve conduction velocity, and HR/HD treatment in such cases frequently alleviates pain and identifies the affected nerve. Thus, our neuropathy model likely mirrors the mild nerve adhesions observed in routine clinical practice, providing a foundation for further research into pain mechanisms. However, the specific effects of HR/HD remain unclear. While previous studies have shown that HD on the median nerve in cadavers reduces nerve gliding resistance, these studies focused on normal nerves. 7 Our study extends this knowledge by demonstrating that HR/HD can also reduce nerve gliding resistance in nerves with adhesions. Future research should investigate the degree to which HR/HD can enhance adhesion and improve clinical outcomes. Limitation The degree of adhesion in the HR/HD group is not fully understood, and it remains unclear to what extent adhesions can be improved by this treatment. To address this, future studies should explore the relationship between ultrasound imaging findings and the degree of adhesions. Additionally, while our sciatic nerve adhesion model maintained normal conduction velocity in the presence of adhesions, it is still uncertain whether this constitutes a pathological neuropathy. Further investigations, including assessments of rat gait and sensory deficits, are necessary to determine whether these factors improve with HR/HD treatment. Conclusion The study demonstrates that ultrasound-guided Hydrorelease/Hydrodissection significantly reduces the gliding resistance of the sciatic nerve in a rat sciatic nerve adhesion model. These findings suggest that HR/HD may be a promising therapeutic approach for improving nerve mobility in conditions characterized by adhesions, potentially leading to better clinical outcomes in patients with similar neuropathic conditions. However, further research is needed to explore the long-term effects of HR/HD, the mechanisms underlying its efficacy, and its applicability in other models of nerve adhesion. Future studies should also investigate the correlation between ultrasound imaging findings and the degree of adhesion improvement to optimize this therapeutic approach. Declarations Ethics approval and consent to participate This study was reviewed and approved by the Animal Experiment Committee of Nissei Bilis Co., Ltd. Shiga Research Institute (Approval Number: 2022-055, 2022-168, 2023-016). The Shiga Research Institute of Nissei Bilis Co., Ltd. has been certified as a facility that complies with the “Basic Guidelines for Conducting Animal Experiments, etc., in Research Institutions under the Jurisdiction of the Ministry of Health, Labour and Welfare” through the External Validation and Accreditation Program for Animal Experiment Facilities conducted by the Japan Pharmaceutical Information Center (JAPIC). Consent for publication Not applicable. Availability of data and materials All relevant data are included in this published article and its Supporting Information files. Competing interests Kazuma Miyatake and Yutaka Inaba received collaborative research funding from Kewpie Corporation. The other authors declare that they have no competing interests. Funding This work received collaborative research funding from Kewpie Corporation. Authors’ contributions Shinya Tsujiku and Yohei Kusaba contributed to the study design, data collection, and initial data analysis. Takuma Naka and Reina Nakamura performed the statistical analysis and contributed to the interpretation of the results. Kazuma Miyatake, Hyounmin Choe, and Yutaka Inaba prepared the manuscript draft and revised it critically for important intellectual content. All authors reviewed and approved the final manuscript. Acknowledgements This research was supported by Kewpie Corporation. We are grateful to members of the Nissei Bilis Co., Ltd. Shiga Research Institute for their important contributions to the experiments. In particular, we extend our sincere gratitude to Researcher Morita for invaluable support and assistance. Authors’ information Not applicable. References Cass SP. Ultrasound-guided nerve hydrodissection: What is it? A review of the literature. Curr Sports Med Rep. 2016;15(1):20-22. doi:10.1249/JSR.0000000000000226. Shojaie P, Botchu R, Iyengar K, et al. Ultrasound-guided median nerve hydrodissection of pronator teres syndrome: A case report and a literature review. J Ultrason. 2023;23(94):e165-e169. doi:10.15557/jou.2023.0026. Wu YT, Chen SR, Li TY, et al. Nerve hydrodissection for carpal tunnel syndrome: A prospective, randomized, double-blind, controlled trial. Muscle Nerve. 2019;59(2):174-180. doi:10.1002/mus.26358. Buntragulpoontawee M, Chang KV, Vitoonpong T, et al. The effectiveness and safety of commonly used injectates for ultrasound-guided hydrodissection treatment of peripheral nerve entrapment syndromes: A systematic review. Front Pharmacol. 2021;11:621150. doi:10.3389/fphar.2020.621150. Omodani T, Takahashi K. Ultrasound-guided hydrodissection for sural neuropathy after calcaneus fracture surgery: A case report. Cureus. 2023;15(10):e47749. doi:10.7759/cureus.47749. Lam KHS, Hung CY, Chiang YP, et al. Ultrasound-guided nerve hydrodissection for pain management: rationale, methods, current literature, and theoretical mechanisms. J Pain Res. 2020;13:1957-1968. doi:10.2147/JPR.S247208. Evers S, Thoreson AR, Smith J, et al. Ultrasound-guided hydrodissection decreases gliding resistance of the median nerve within the carpal tunnel. Muscle Nerve. 2018;57(1):25-32. doi:10.1002/mus.25723. Abe Y, Doi K, Sakai K, et al. Experimental study of the peripheral nerve excursion. J Jpn Soc Surg Hand. 1994;11(4):480-484. (in Japanese). Ikeda K, Yamauchi D, Osamura N, et al. Hyaluronic acid prevents peripheral nerve adhesion. Br J Plast Surg. 2003;56(4):342-347. doi:10.1016/S0007-1226(03)00197-8. Walton MJ, Mackie K, Fallon M, et al. The reliability and validity of magnetic resonance imaging in the assessment of chronic lateral epicondylitis. J Hand Surg Am. 2011;36(3):475-479. doi:10.1016/j.jhsa.2010.11.040. Table Table 1 is available in the supplementary files section Additional Declarations No competing interests reported. Supplementary Files Additionalfile1rawindividualleveldata.xlsx Additionalfile2analysisnotesandvariabledefinitions.xlsx table1.jpg Table 1：The degree of adhesions after surgery The degree of adhesions observed during gross evaluation progressed over time after surgery. Cite Share Download PDF Status: Published Journal Publication published 07 Apr, 2026 Read the published version in Journal of Orthopaedic Surgery and Research → Version 1 posted Editorial decision: Revision requested 19 Jan, 2026 Editor assigned by journal 18 Jan, 2026 Submission checks completed at journal 18 Jan, 2026 First submitted to journal 17 Jan, 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-8624003","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":576665808,"identity":"55b96035-fd11-49ad-8c8b-1a6143b9c3d3","order_by":0,"name":"Kazuma 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1","display":"","copyAsset":false,"role":"figure","size":754803,"visible":true,"origin":"","legend":"\u003cp\u003eCreation of a rat sciatic nerve adhesion model\u003c/p\u003e\n\u003cp\u003eAn incision was made on the right thigh to expose the sciatic nerve, which was then dissected. The nerve beds were coagulated using an electrocautery device. Both ends of the sciatic nerve were fixed to the nerve bed using 8-0 nylon sutures.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/870299091ad9352012f7cacc.png"},{"id":100667251,"identity":"a2cc3f63-f426-4073-a8c9-25a11f5c6a1a","added_by":"auto","created_at":"2026-01-20 09:46:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":260495,"visible":true,"origin":"","legend":"\u003cp\u003eGross evaluation of the degree of adhesion\u003c/p\u003e\n\u003cp\u003eStage 0: No adhesion\u003c/p\u003e\n\u003cp\u003eStage 1: A thin film on the nerve surface and mild adhesion observed\u003c/p\u003e\n\u003cp\u003eStage 2: Scar tissue around the nerve with moderate adhesion observed\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/79bb5429fe9bf3b4f99f8899.png"},{"id":100667442,"identity":"b1e6fb1f-a89f-4872-a1f5-062f0401db18","added_by":"auto","created_at":"2026-01-20 09:46:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":334420,"visible":true,"origin":"","legend":"\u003cp\u003eBiomechanical examination\u003c/p\u003e\n\u003cp\u003eThe sciatic nerve was pulled vertically, to measure the tensile strength required to detach it from the nerve bed by a digital force gauge.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/34392184132e9e6e4d55dd89.png"},{"id":100667347,"identity":"0307f23e-0132-458f-987c-151bf1176ef3","added_by":"auto","created_at":"2026-01-20 09:46:29","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":379892,"visible":true,"origin":"","legend":"\u003cp\u003eElectrophysiological evaluation\u003c/p\u003e\n\u003cp\u003eRats were evaluated at 6 weeks post-surgery for nerve conduction velocity. Stimulation electrodes were placed near the sciatic nerve, Achilles tendon, and plantar muscle. Electrical stimulation was applied, and potentials were recorded with a polygraph system.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/d980624e40251e1368778b45.png"},{"id":100667390,"identity":"eea48001-2a73-487c-9f4f-c42053c46d55","added_by":"auto","created_at":"2026-01-20 09:46:34","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":408083,"visible":true,"origin":"","legend":"\u003cp\u003eUltrasound-guided Hydrorelease/Hydrodissection for a Rat Sciatic Nerve\u003c/p\u003e\n\u003cp\u003eHR/HD was performed using ultrasound guidance. The procedure involved the circumferential dissection of the paraneural sheath around the nerve bed.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/c843b95602bbc9ff9f3eaac3.png"},{"id":100666961,"identity":"e6b898cc-2590-47f7-8ea4-e670ac722e5a","added_by":"auto","created_at":"2026-01-20 09:44:19","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":392934,"visible":true,"origin":"","legend":"\u003cp\u003eA rat sciatic nerve adhesion model (Stage1)\u003c/p\u003e\n\u003cp\u003eThe nerve bedswere coagulated using an electrocautery device. Both ends of the sciatic nerve were fixed to the nerve bed using 8-0 nylon sutures. After 6 weeks, a thin film on the sciatic nerve surface and mild adhesion observed.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/45ed0429ca2388f791d9e968.png"},{"id":100667133,"identity":"43aecddc-64e1-4b83-95f3-6f2fc401c8d0","added_by":"auto","created_at":"2026-01-20 09:45:37","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":48609,"visible":true,"origin":"","legend":"\u003cp\u003eAdhesions progressed over time post-surgery\u003c/p\u003e\n\u003cp\u003eThe tensile strength at 3 and 6 weeks was significantly higher than that at earlier stages. (P \u0026lt; 0.05)\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/b175dd62deef8e5755ff8aff.png"},{"id":100667261,"identity":"0d609fe8-cf2f-4ff1-bc68-887a7e5263c5","added_by":"auto","created_at":"2026-01-20 09:46:12","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":25769,"visible":true,"origin":"","legend":"\u003cp\u003ePost-operative electrophysiological evaluation after 6weeks No significant difference in latency was observed between the adhesion and healthy groups.\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/61867df889075038033cbad8.png"},{"id":100666956,"identity":"2b5bb2ea-e95c-42e5-ad2f-db9bbc0124bb","added_by":"auto","created_at":"2026-01-20 09:44:16","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":27017,"visible":true,"origin":"","legend":"\u003cp\u003eEffect of ultrasound-guided hydrorelease/hydrodissection on adhesions\u003c/p\u003e\n\u003cp\u003eUltrasound-guided HR/HD significantly reduces the gliding resistance of the sciatic nerve in a rat sciatic nerve adhesion model. (P \u0026lt; 0.05)\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/505e3ba2a73529701a62977f.png"},{"id":106809294,"identity":"37648bbf-af4a-4923-9cca-935ed8a9b0b4","added_by":"auto","created_at":"2026-04-13 16:09:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4126013,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/c7792230-5918-403b-a2a8-39e0b333c7c9.pdf"},{"id":100667116,"identity":"e93a14f2-fa71-46c6-b8bd-d26fc0222474","added_by":"auto","created_at":"2026-01-20 09:45:29","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13379,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile1rawindividualleveldata.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/0572aa9f5c47cb4681e6df22.xlsx"},{"id":100667159,"identity":"cb86ce01-2f04-4a79-ad7d-7718f8085b54","added_by":"auto","created_at":"2026-01-20 09:45:45","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":10637,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile2analysisnotesandvariabledefinitions.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/4d24625faa26fdaffa692fd8.xlsx"},{"id":100667007,"identity":"ed45b3dc-9d7d-4676-b6b4-92ac37f704d5","added_by":"auto","created_at":"2026-01-20 09:44:32","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":28193,"visible":true,"origin":"","legend":"\u003cp\u003eTable 1：The degree of adhesions after surgery\u003c/p\u003e\n\u003cp\u003eThe degree of adhesions observed during gross evaluation progressed over time after surgery.\u003c/p\u003e","description":"","filename":"table1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8624003/v1/5d88967c5b447d05db7eb9a6.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Ultrasound-guided Hydrorelease/Hydrodissection Reduces Gliding Resistance in a Rat Sciatic Nerve Adhesion Model : a preclinical experimental study","fulltext":[{"header":"Background","content":"\u003cp\u003ePeripheral nerve entrapment (for example carpal tunnel syndrome, cubital tunnel syndrome ...etc) is a common condition encountered in daily clinical practice. Treatment options for peripheral nerve entrapment include surgical intervention and pharmacological therapy, with injections serving as a viable alternative. With advancements in ultrasonography, the visualization of peripheral nerves has greatly improved, leading to increased use of nerve hydrodissection (HD) as a treatment for peripheral nerve entrapment. HD involves the injection of a solution, such as an anesthetic or saline, to separate the nerve from surrounding tissues, including fascia or adjacent structures, thereby alleviating entrapment and associated symptoms.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn Asia, the term \"hydrorelease\" (HR) has become widely adopted to describe a similar technique targeting peripheral nerves. While both HD and HR are used to treat nerve entrapment, the precise mechanisms and comparative efficacy of these techniques remain subjects of ongoing investigation. HD has been applied successfully to various nerves, including the median, ulnar, sural, and nerve roots, demonstrating its versatility in clinical practice.\u003csup\u003e\u003cspan additionalcitationids=\"CR3 CR4 CR5\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e–\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe choice of solution in HD, whether saline, 5% glucose, or other substances,\u003csup\u003e4\u003c/sup\u003e has sparked debate, with some evidence suggesting that the physical separation of tissues plays a key role in pain relief. A cadaveric study from the Mayo Clinic supports this theory, showing that HD reduces the gliding resistance of the median nerve within the carpal tunnel, indicating beneficial mechanical changes in nerve movement.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eDespite these advancements, the effects of HD on nerve gliding, particularly in cases of nerve adhesions, are not fully understood. To address this gap, we developed a mild adhesion model of the rat sciatic nerve to investigate the potential of HD/HR to improve nerve compromised by adhesions. We hypothesize that HD/HR will enhance the gliding of the sciatic nerve affected by adhesions, offering insights into its therapeutic potential.\u003c/p\u003e \n\n \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\n \u003cp\u003e \u003c/p\u003e \n\n \u003cp\u003e \u003c/p\u003e\n\n "},{"header":"Methods","content":"\u003ch3\u003eExperiment 1: Creation of a Rat Sciatic Nerve Adhesion Model\u003c/h3\u003e\u003cp\u003eWe created a rat sciatic nerve adhesion model based on the rabbit model described by Abe et al., choosing rats due to their easier handling..\u003csup\u003e8,9\u003c/sup\u003e The procedure involved the following steps in the right thigh of each rat (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), with the left thigh serving as an untreated control.\u003c/p\u003e\u003cp\u003e1. A mixed anesthetic( Medetomidine Hydrochloride: 0.06 mg/mL, Midazolam: 0.8 mg/mL, Butorphanol Tartrate: 1 mg/mL) was administered subcutaneously to anesthetize the rats (2.5 mL/kg). 2. After shaving the right thigh, the surgical area was disinfected with ethanol and povidone-iodine (10% Povidone-Iodine Solution, Yoshida Pharmaceutical Co., Ltd.). 3. An incision was made on the right thigh to expose the sciatic nerve, which was then dissected, and the nerve beds were coagulated using an electrocautery device. 4. Both ends of the sciatic nerve were fixed to the nerve bed using 8 − 0 nylon sutures. 5. The muscles and skin were sutured separately. 6. The sutured area was disinfected with povidone-iodine, and atipamezole hydrochloride solution (2.5 mL) was administered subcutaneously before returning the animals to their cages.\u003c/p\u003e\u003ch2\u003eEvaluation of the Degree of Adhesion (Gross Evaluation and Biomechanical examination)\u003c/h2\u003e\u003cp\u003eFor the 1-, 3-, and 6-week evaluation groups, the following procedures were conducted: 1 week (n = 6), 3 weeks (n = 6), and 6 weeks (n = 7) after the creation of the nerve adhesion model. The sciatic nerve on the contralateral side (n = 7) served as the control for comparative analysis.\u003c/p\u003e\u003cp\u003eRats were euthanized under isoflurane anesthesia using the arteriovenous transection method. An incision was made in the right thigh to visually inspect the degree of adhesion between the sciatic nerve and the surrounding tissues. Photographs were taken with a digital camera for documentation. Adhesion was evaluated as follows: stage 0, no adhesion; stage 1, a thin film on the nerve surface and mild adhesion observed; and stage 2, scar tissue around the nerve with moderate adhesion observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Two examiners independently classified the cases, and in instances where their assessments differed, a consensus was reached through discussion. Biomechanical examination was performed following the method described by Ikeda et al.\u003csup\u003e9\u003c/sup\u003e The distal portion of the sciatic nerve and sutures in the right thigh were removed. The sciatic nerve was then tied to a digital force gauge (DST-20N, Imada Co., Ltd.) using a 3 − 0 silk thread. The gauge was placed 5 cm from the nerve, and the sciatic nerve was pulled vertically to measure the tensile strength required to detach it from the nerve bed (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003ch3\u003eElectrophysiological Evaluation\u003c/h3\u003e\u003cp\u003eBased on the results from the adhesion model, rats (n = 6) were evaluated 6 weeks post-surgery. Sodium secobarbital (Ional-sodium, Nippon Chemiphar Co., Ltd.) at 50 mg/kg was administered intraperitoneally to anesthetize the rats. The lumbar and dorsal areas were shaved, and the animals were placed in a prone position. Stimulation electrodes (needle electrodes, Unique Medical Co., Ltd.) were positioned near the sciatic nerve (for distal stimulation), near the Achilles tendon (for proximal stimulation), and in the plantar muscle (for recording) of each hind limb (right (n = 6), adhesion side; left (n = 6), contralateral side) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Body temperature was maintained within the range of 37–38°C. Rectangular wave stimulation (1 Hz, 0.1 msec, submax voltage) was delivered using an electrical stimulator (SEN-3301 or SEN-3401MG, Nihon Kohden Corporation) to the distal and proximal stimulation electrodes. The elicited potentials were recorded by the recording electrode and input into a polygraph system (RMT-1000, Nihon Kohden Corporation) via a bioelectric amplifier (PB-101H, Nihon Kohden Corporation).\u003c/p\u003e\u003cp\u003eNerve conduction velocity was calculated based on the conduction times from both the distal and proximal sites and the distance between the electrodes. The amplitude of the M-wave was measured using analysis software (LabChart, ADInstruments). This measurement was repeated three times with sufficient rest between each measurement, and the average value was used.\u003c/p\u003e\u003ch3\u003eExperiment 2: Ultrasound-guided Hydrorelease/Hydrodissection for a Rat Sciatic Nerve Adhesion Model\u003c/h3\u003e\u003cp\u003eBased on results from Experiment 1, rats (n = 7) were used at 6 weeks post-surgery. Under isoflurane anesthesia (Isoflurane Inhalation Anesthetic 'VTRS,’ Mylan EPD G.K.), HR/HD was performed using ultrasound guidance. An experienced physician utilized a general-purpose ultrasound diagnostic device (Aplio i900; Canon Medical Systems Corporation) to visualize the sciatic nerve in the right thigh. The nerve was displayed in a single-axis image without piercing it. The procedure involved the circumferential dissection of the paraneural sheath around the nerve bed (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). A total of 2 mL of saline was used as the dissection solution to sufficiently separate the nerve.\u003c/p\u003e\u003ch3\u003eEvaluation of the Degree of Adhesion (Gross Evaluation and Biomechanical Examination)\u003c/h3\u003e\u003cp\u003eGross evaluation and biomechanical examination were conducted a day after injection using the same methods as in Experiment 1. The results were compared to those of Experiment 1.\u003c/p\u003e\u003cp\u003eRaw individual-level data and variable definitions are provided as Supplementary Information (Additional files 1–2).\u003c/p\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eThe results of the distal CMAP, proximal CMAP, and nerve conduction velocity in the non-adhesion and 6-week post-operative adhesion groups were analyzed using one-way analysis of variance (ANOVA). Comparisons of tensile strength among the non-adhesion, 1-week, 3-week, and 6-week post-operative groups were performed using Tukey’s test. Inter-observer agreement for visual adhesion assessment was evaluated using Kendall’s coefficient of concordance. Comparisons between the untreated 6-week adhesion group (Experiment 1) and the adhesion + HR/HD group (Experiment 2) were unpaired because different animals were used in each group.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eGross Evaluation and Biomechanical Examination (Experiment 1)\u003c/h2\u003e \u003cp\u003eOf the 26 cases, consensus between the evaluators was achieved in 23 instances, while three cases required further discussion for classification. The Kendall\u0026rsquo;s coefficient of concordance was 0.92, indicating high agreement between evaluators. All healthy side adhesions (n\u0026thinsp;=\u0026thinsp;7) were classified as stage 0. At 1 week post-operation, the distribution was as follows: stage 0 (3 cases), stage 1 (2 cases), and stage 2 (1 case). By 3 weeks, the distribution shifted to stage 0 (0 cases), stage 1 (3 cases), and stage 2 (3 cases). At 6 weeks, the majority were classified as stage 2 (5 cases), with the remaining two cases at stage 1, showing a clear progression of adhesion severity over time (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e)(Table\u0026nbsp;1). The biomechanical examination revealed a significant increase in tensile strength over time: 0.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 N (no adhesion), 1.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29 N (1 week), 1.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 N (3 weeks), 3.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18 N (6 weeks). Notably, the tensile strength at 3 and 6 weeks was significantly higher than that at earlier stages (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). (figure.7)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eElectrophysiological Evaluation (Experiment 1)\u003c/h3\u003e\n\u003cp\u003eThe latency in the healthy group was 38.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.75 m/sec, compared to 41.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.17 m/sec in the adhesion group. Despite the differences in values, no significant difference in latency was observed between the adhesion and healthy groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEffect of HR/HD on Adhesions (Experiments 1 and 2)\u003c/h2\u003e \u003cp\u003eIn the Adhesion་HR/HD group, post-operative adhesion stages were classified as stage 1 in 3 cases and stage 2 in 4 cases. The tensile strength required to detach the sciatic nerve in the presence of adhesions plus HR/HD treatment was 2.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16 N (n\u0026thinsp;=\u0026thinsp;7) (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e). Compared to the untreated adhesion group, HR/HD treatment significantly reduced tensile strength (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, the tensile strength remained slightly higher than in the no-adhesion group, indicating that the treatment did not fully revert the condition to a state of no adhesion. The untreated adhesion group and the adhesion\u0026thinsp;+\u0026thinsp;HR/HD group consisted of different animals.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe successfully developed a model in which adhesions progressively worsened over the post-operative weeks. This model effectively replicates the mild neuropathy often observed in clinical practice, as it induces a mild degree of adhesion while maintaining normal nerve conduction velocity. Furthermore, in the sciatic nerve adhesion model, HR/HD demonstrated a reduction in tensile strength and an improvement in nerve gliding, even in nerves that had developed adhesions.\u003c/p\u003e \u003cp\u003eOur model, characterized by a robust adhesion at 6 weeks postoperatively, demonstrates that adhesions increase in severity over time. Adhesion assessment is commonly performed using Petersen's classification, which evaluates wound healing and the actual detachment of the nerve during dissection. In this study, we developed a visual adhesion assessment method with high inter-rater reliability. Future studies should aim to develop models with stronger adhesions and create a more detailed classification system, incorporating histological evaluations to enhance accuracy.\u003c/p\u003e \u003cp\u003eIn nerve conduction velocity tests, severe adhesions were associated with decreases in CMAP and MCV. However, the variability in adhesion severity can lead to a mixture of normal and abnormal nerve conduction velocities. Our model, which achieved milder adhesions by minimizing ablation of the nerve bed and targeting only the regions in contact with the nerve, successfully maintained normal nerve conduction velocity. This finding contrasts with previous reports and suggests that our model more accurately represents mild neuropathies frequently encountered in clinical practice. Moreover, HR/HD is known to be more effective in treating mild to moderate neuropathies than severe ones.\u003csup\u003e11\u003c/sup\u003e In daily practice, patients often present with nerve-origin pain without abnormalities in imaging or nerve conduction velocity, and HR/HD treatment in such cases frequently alleviates pain and identifies the affected nerve. Thus, our neuropathy model likely mirrors the mild nerve adhesions observed in routine clinical practice, providing a foundation for further research into pain mechanisms.\u003c/p\u003e \u003cp\u003eHowever, the specific effects of HR/HD remain unclear. While previous studies have shown that HD on the median nerve in cadavers reduces nerve gliding resistance, these studies focused on normal nerves.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Our study extends this knowledge by demonstrating that HR/HD can also reduce nerve gliding resistance in nerves with adhesions. Future research should investigate the degree to which HR/HD can enhance adhesion and improve clinical outcomes.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eLimitation\u003c/h2\u003e \u003cp\u003eThe degree of adhesion in the HR/HD group is not fully understood, and it remains unclear to what extent adhesions can be improved by this treatment. To address this, future studies should explore the relationship between ultrasound imaging findings and the degree of adhesions. Additionally, while our sciatic nerve adhesion model maintained normal conduction velocity in the presence of adhesions, it is still uncertain whether this constitutes a pathological neuropathy. Further investigations, including assessments of rat gait and sensory deficits, are necessary to determine whether these factors improve with HR/HD treatment.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe study demonstrates that ultrasound-guided Hydrorelease/Hydrodissection significantly reduces the gliding resistance of the sciatic nerve in a rat sciatic nerve adhesion model. These findings suggest that HR/HD may be a promising therapeutic approach for improving nerve mobility in conditions characterized by adhesions, potentially leading to better clinical outcomes in patients with similar neuropathic conditions. However, further research is needed to explore the long-term effects of HR/HD, the mechanisms underlying its efficacy, and its applicability in other models of nerve adhesion. Future studies should also investigate the correlation between ultrasound imaging findings and the degree of adhesion improvement to optimize this therapeutic approach.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;This study was reviewed and approved by the Animal Experiment Committee of Nissei Bilis Co., Ltd. Shiga Research Institute (Approval Number: 2022-055, 2022-168, 2023-016). The Shiga Research Institute of Nissei Bilis Co., Ltd. has been certified as a facility that complies with the “Basic Guidelines for Conducting Animal Experiments, etc., in Research Institutions under the Jurisdiction of the Ministry of Health, Labour and Welfare” through the External Validation and Accreditation Program for Animal Experiment Facilities conducted by the Japan Pharmaceutical Information Center (JAPIC).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;All relevant data are included in this published article and its Supporting Information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Kazuma Miyatake and Yutaka Inaba received collaborative research funding from Kewpie Corporation. The other authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;This work received collaborative research funding from Kewpie Corporation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Shinya Tsujiku and Yohei Kusaba contributed to the study design, data collection, and initial data analysis. Takuma Naka and Reina Nakamura performed the statistical analysis and contributed to the interpretation of the results. Kazuma Miyatake, Hyounmin Choe, and Yutaka Inaba prepared the manuscript draft and revised it critically for important intellectual content. All authors reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;This research was supported by Kewpie Corporation. We are grateful to members of the Nissei Bilis Co., Ltd. Shiga Research Institute for their important contributions to the experiments. In particular, we extend our sincere gratitude to Researcher Morita for invaluable support and assistance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ information\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCass SP. Ultrasound-guided nerve hydrodissection: What is it? A review of the literature. Curr Sports Med Rep. 2016;15(1):20-22. doi:10.1249/JSR.0000000000000226.\u003c/li\u003e\n\u003cli\u003eShojaie P, Botchu R, Iyengar K, et al. Ultrasound-guided median nerve hydrodissection of pronator teres syndrome: A case report and a literature review. J Ultrason. 2023;23(94):e165-e169. doi:10.15557/jou.2023.0026.\u003c/li\u003e\n\u003cli\u003eWu YT, Chen SR, Li TY, et al. Nerve hydrodissection for carpal tunnel syndrome: A prospective, randomized, double-blind, controlled trial. Muscle Nerve. 2019;59(2):174-180. doi:10.1002/mus.26358.\u003c/li\u003e\n\u003cli\u003eBuntragulpoontawee M, Chang KV, Vitoonpong T, et al. The effectiveness and safety of commonly used injectates for ultrasound-guided hydrodissection treatment of peripheral nerve entrapment syndromes: A systematic review. Front Pharmacol. 2021;11:621150. doi:10.3389/fphar.2020.621150.\u003c/li\u003e\n\u003cli\u003eOmodani T, Takahashi K. Ultrasound-guided hydrodissection for sural neuropathy after calcaneus fracture surgery: A case report. Cureus. 2023;15(10):e47749. doi:10.7759/cureus.47749.\u003c/li\u003e\n\u003cli\u003eLam KHS, Hung CY, Chiang YP, et al. Ultrasound-guided nerve hydrodissection for pain management: rationale, methods, current literature, and theoretical mechanisms. J Pain Res. 2020;13:1957-1968. doi:10.2147/JPR.S247208.\u003c/li\u003e\n\u003cli\u003eEvers S, Thoreson AR, Smith J, et al. Ultrasound-guided hydrodissection decreases gliding resistance of the median nerve within the carpal tunnel. Muscle Nerve. 2018;57(1):25-32. doi:10.1002/mus.25723.\u003c/li\u003e\n\u003cli\u003eAbe Y, Doi K, Sakai K, et al. Experimental study of the peripheral nerve excursion. J Jpn Soc Surg Hand. 1994;11(4):480-484. (in Japanese).\u003c/li\u003e\n\u003cli\u003eIkeda K, Yamauchi D, Osamura N, et al. Hyaluronic acid prevents peripheral nerve adhesion. Br J Plast Surg. 2003;56(4):342-347. doi:10.1016/S0007-1226(03)00197-8.\u003c/li\u003e\n\u003cli\u003eWalton MJ, Mackie K, Fallon M, et al. The reliability and validity of magnetic resonance imaging in the assessment of chronic lateral epicondylitis. J Hand Surg Am. 2011;36(3):475-479. doi:10.1016/j.jhsa.2010.11.040.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1 is available in the supplementary files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-orthopaedic-surgery-and-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"josr","sideBox":"Learn more about [Journal of Orthopaedic Surgery and Research](http://josr-online.biomedcentral.com)","snPcode":"13018","submissionUrl":"https://submission.nature.com/new-submission/13018/3","title":"Journal of Orthopaedic Surgery and Research","twitterHandle":"@MSKmedBMC","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Adhesion of Peripheral nerve, Nerve hydrodissection (HD), Hydrorelease (HR), Nerve gliding resistance, Tensile strength","lastPublishedDoi":"10.21203/rs.3.rs-8624003/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8624003/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eUltrasound-guided nerve hydrodissection (HD), often referred to as hydrorelease (HR) in Asia, is increasingly used for peripheral nerve entrapment. Although HD/HR is clinically applied to separate nerves from surrounding tissues and potentially improve symptoms, its mechanical effects on nerve mobility under perineural adhesions remain incompletely understood. This study aimed to establish a mild rat sciatic nerve adhesion model and to evaluate whether ultrasound-guided HR/HD improves nerve gliding without impairing nerve function.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA rat sciatic nerve adhesion model was created in the right thigh by exposing the sciatic nerve, coagulating the nerve bed, and fixing both ends of the nerve to the bed with 8\u0026thinsp;\u0026minus;\u0026thinsp;0 nylon sutures; the contralateral side served as control. Adhesion severity was assessed macroscopically at 1, 3, and 6 weeks (stage 0\u0026ndash;2) by two examiners, and tensile strength required to detach the nerve from the bed was measured using a digital force gauge. Nerve function at 6 weeks was evaluated by nerve conduction studies (CMAP and motor nerve conduction velocity). Based on model characterization, ultrasound-guided HR/HD was performed at 6 weeks using 2 mL saline to circumferentially dissect the paraneural sheath, and gross adhesion and tensile strength were reassessed one day after injection. Statistical analyses included one-way ANOVA, Tukey\u0026rsquo;s test, and Kendall\u0026rsquo;s coefficient of concordance.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAdhesions progressed over time, with most nerves showing stage 2 adhesions at 6 weeks; inter-observer agreement was high (Kendall\u0026rsquo;s coefficient 0.92). Tensile strength increased with time (0.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 N in controls; 1.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29 N at 1 week; 1.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 N at 3 weeks; 3.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18 N at 6 weeks), with significantly higher values at 3 and 6 weeks compared with earlier time points (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Motor nerve conduction parameters at 6 weeks did not differ significantly between adhesion and control sides. Ultrasound-guided HR/HD significantly reduced tensile strength in the adhesion model (2.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16 N; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs untreated adhesions), although values remained higher than controls.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn a rat sciatic nerve adhesion model with preserved nerve conduction, ultrasound-guided HR/HD reduced tensile strength required to detach the nerve from the bed, indicating improved mechanical mobility/gliding under adhesions. These findings support HR/HD as a minimally invasive approach to enhance nerve gliding in mild perineural adhesion conditions and warrant further studies on long-term outcomes and imaging\u0026ndash;pathology correlations.\u003c/p\u003e","manuscriptTitle":"Ultrasound-guided Hydrorelease/Hydrodissection Reduces Gliding Resistance in a Rat Sciatic Nerve Adhesion Model : a preclinical experimental study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-20 08:40:10","doi":"10.21203/rs.3.rs-8624003/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-19T08:39:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-18T21:29:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-18T21:29:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Orthopaedic Surgery and Research","date":"2026-01-17T06:40:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-orthopaedic-surgery-and-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"josr","sideBox":"Learn more about [Journal of Orthopaedic Surgery and Research](http://josr-online.biomedcentral.com)","snPcode":"13018","submissionUrl":"https://submission.nature.com/new-submission/13018/3","title":"Journal of Orthopaedic Surgery and Research","twitterHandle":"@MSKmedBMC","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"329776f7-0cd8-4c0a-86b0-7224a84f73a4","owner":[],"postedDate":"January 20th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-13T16:05:01+00:00","versionOfRecord":{"articleIdentity":"rs-8624003","link":"https://doi.org/10.1186/s13018-026-06816-1","journal":{"identity":"journal-of-orthopaedic-surgery-and-research","isVorOnly":false,"title":"Journal of Orthopaedic Surgery and Research"},"publishedOn":"2026-04-07 15:58:24","publishedOnDateReadable":"April 7th, 2026"},"versionCreatedAt":"2026-01-20 08:40:10","video":"","vorDoi":"10.1186/s13018-026-06816-1","vorDoiUrl":"https://doi.org/10.1186/s13018-026-06816-1","workflowStages":[]},"version":"v1","identity":"rs-8624003","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8624003","identity":"rs-8624003","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}