The limited role of serum neurofilament light chain in predicting pain severity of patients with diabetic polyneuropathy.

Pain is one of many complaints expressed by patients with diabetic polyneuropathy. However, no objective measure for pain severity has been available. Neurofilament light chains have been widely used for assessing axonal damage in the neuronal system. Hence, we sought to investigate whether neurofilament light chains can serve as a marker reflecting pain severity in diabetic polyneuropathy. We enrolled the patients with diabetic polyneuropathy. Serum concentrations of neurofilament light chain were then measured using a single-molecule array. Pain severity was evaluated using painDETECT and the Brief Pain Inventory. Moreover, laboratory results including, serum creatinine, HbA1c, and glomerular filtration rate. A correlation test was used to analyze each variable. A total of 42 patients were enrolled. Neurofilament light chain levels were unable to reflect current neuropathic pain severity. However, high levels of neurofilament light chain were a significant predictor of poor diabetes control (r = 0.41; p = 0.02) and kidney damage (r = 0.45; p = 0.01). Serum levels of neurofilament light chain could not reflect current pain severity but was strongly associated with kidney dysfunction and poor diabetes control. Other biomarkers that could predict pain severity need to be uncovered.

Efficacy of 3D printed anatomically equivalent thermoplastic polyurethane guide conduits in promoting the regeneration of critical-sized peripheral nerve defects.

Three-dimensional (3D) printing is an emerging tool for creating patient-specific tissue constructs analogous to the native tissue microarchitecture. In this study, anatomically equivalent 3D nerve conduits were developed using thermoplastic polyurethane (TPU) by combining reverse engineering and material extrusion (i.e., fused deposition modeling) technique. Printing parameters were optimized to fabricate nerve-equivalent TPU constructs. The TPU constructs printed with different infill densities supported the adhesion, proliferation, and gene expression of neuronal cells. Subcutaneous implantation of the TPU constructs for three months in rats showed neovascularization with negligible local tissue inflammatory reactions and was classified as a non-irritant biomaterial as per ISO 10993-6. To perform in vivo efficacy studies, nerve conduits equivalent to rat's sciatic nerve were fabricated and bridged in a 10 mm sciatic nerve transection model. After four months of implantation, the sensorimotor function and histological assessments revealed that the 3D printed TPU conduits promoted the regeneration in critical-sized peripheral nerve defects equivalent to autografts. This study proved that TPU-based 3D printed nerve guidance conduits can be created to replicate the complicated features of natural nerves that can promote the regeneration of peripheral nerve defects and also show the potential to be extended to several other tissues for regenerative medicine applications. .

Changes in Compression Pressure of Elastic Stockings for the Lower Limbs During Cesarean Section: A Prospective Observational Study.

Background Postpartum peripheral nerve injuries can impact recovery. Elastic stockings are recommended for thromboembolism prevention, although concerns about entrapment neuropathy exist. In this prospective observational study, we investigated the differential compressions caused by wearing elastic stockings before and after anesthesia, as well as changes in the diameters of the lower leg and ankle in parturient women undergoing spinal anesthesia for elective cesarean section (CS). Methods Eighteen pregnant women, classified by the American Society of Anesthesiologists as having physical status 2, underwent lower leg measurements taken before a CS. Elastic stockings were applied, and compression pressure was measured at pre-anesthesia, post-surgery, and six hours post-return to a hospital room. Fluid, blood loss, urine output, and neuropathy presence were recorded. For all parameters, changes at the three time points were compared for the primary analysis. For secondary analysis, participants were categorized as having intraoperative blood loss greater than (group P) or less than 1,000 g (group N), and factors were compared with pre-anesthesia and six hours post-return to a room. Data were analyzed and presented using a one-way analysis of variance with Bonferroni correction for multiple comparisons or unpaired two-tailed t-tests for pairwise comparison. Results None of the women had postoperative entrapment neuropathy. Six patients had >1,000 g of blood loss. Compression significantly increased from pre-anesthesia (left 13.6 ± 2.4, 95% CI: 12.18 to 14.52; right 13.4 ± 2.4, 95% CI: 12.41 to 14.69) to post-surgery (left, 17.4 ± 2.6, 95% CI: 15.68 to 18.12; right, 16.9 ± 2.6, 95% CI: 16.20 to 18.70) (p < 0.01). Compression pressure at post-surgery differed significantly between group P (left, 15.3 ± 1.3; right, 14.7 ± 1.8; 95% CI: -4.98 to -0.32) and group N (left, 18.1 ± 2.9; right, 17.8 ± 2.4; 95% CI: -5.38 to -0.26) (p < 0.05). The results are expressed as mean ± standard deviation, with P-values <0.05 indicating statistical significance. Conclusions In this study, no neuropathy occurred; however, over-compression risk with elastic stockings, especially when exceeding recommended pressure levels, was highlighted. Balancing thromboembolism prevention and over-compression risks is crucial for patients undergoing CSs with spinal anesthesia.

Spinal cord stimulation attenuates paclitaxel-induced gait impairment and mechanical hypersensitivity via peripheral neuroprotective mechanisms in tumor-bearing rats.

BACKGROUND: Taxanes such as paclitaxel (PTX) induce dose-dependent chemotherapy-induced peripheral neuropathy (CIPN), which is associated with debilitating chronic pain and gait impairment. Increased macrophage-related proinflammatory activities have been reported to mediate the development and maintenance of neuropathic pain. While spinal cord stimulation (SCS) has been used for a number of pain conditions, the mechanisms supporting its use for CIPN remain to be elucidated. Thus, we aimed to examine whether SCS can attenuate Schwann cell-mediated and macrophage-mediated neuroinflammation in the sciatic nerve of Rowlette Nude (RNU) rats with PTX-induced gait impairment and mechanical hypersensitivity. METHODS: Adult male tumor-bearing RNU rats were used for this study examining PTX treatment and SCS. Gait and mechanical hypersensitivity were assessed weekly. Cytokines, gene expression, macrophage infiltration and polarization, nerve morphology and Schwann cells were examined in sciatic nerves using multiplex immunoassay, bulk RNA sequencing, histochemistry and immunohistochemistry techniques. RESULTS: SCS (50 Hz, 0.2 milliseconds, 80% motor threshold) attenuated the development of mechanical hypersensitivity (20.93±0.80 vs 12.23±2.71 grams, p<0.0096) and temporal gait impairment [swing (90.41±7.03 vs 117.27±9.71%, p<0.0076), and single stance times (94.92±3.62 vs 112.75±7.27%, p<0.0245)] induced by PTX (SCS+PTX+Tumor vs Sham SCS+PTX+Tumor). SCS also attenuated the reduction in Schwann cells, myelin thickness and increased the concentration of anti-inflammatory cytokine interleukin (IL)-10. Bulk RNA sequencing revealed differential gene expression after SCS, with 607 (59.2%) genes upregulated while 418 (40.8%) genes were downregulated. Notably, genes related to anti-inflammatory cytokines and neuronal growth were upregulated, while genes related to proinflammatory-promoting genes, increased M2γ polarization and decreased macrophage infiltration and Schwann cell loss were downregulated. CONCLUSION: SCS may attenuate PTX-induced pain and temporal gait impairment, which may be partly attributed to decreases in Schwann cell loss and macrophage-mediated neuroinflammation in sciatic nerves.

The reliability and applicability of the Ten Test in hand injuries: A systematic review.

Introduction: The Ten Test (TT) is a touch threshold test that quantifies sensory discrimination by comparing an injured area with a contralateral uninjured area. It's quick, simple, equipment-free and repeatable. However, as a subjective measure, the TT's reliability and applicability need further investigation. This review aimed to investigate if the TT has superior inter- and intra-examiner reliability compared to the widely accepted Weinstein Enhanced Sensory Test (WEST) in a human population of all ages. Methods: A systematic search was conducted on major databases from January 1997 to September 2023 and adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. Outcomes were assessed with a narrative approach. The included articles were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies two tool. Results: This review included five articles. High inter-examiner reliability was demonstrated with intraclass correlation coefficient (ICC) values of 0.91 and 0.95, alongside a kappa statistic of 1, as reported by three distinct studies. Intra-examiner reliability displayed some variance, with one study reporting a significant ICC value in four out of six instances. Two studies corroborated that the TT results corresponded with the findings of WEST, each presenting a Spearman rank coefficient of -0.71. Conclusion: Our findings underscore the TT's high inter-examiner reliability, though its intra-examiner reliability exhibited some inconsistencies. Interestingly, certain studies claimed its superiority over the WEST. To validate the TT's use in the clinical setting, more rigorous studies, particularly those comparing pre-operative TT outcomes with intraoperative nerve damage evaluations, are essential.

Nerve Regeneration after a Nerve Graft in a Rat Model: The Effectiveness of Fibrin Glue.

BACKGROUND: Simulating the post-traumatic continuity defect of small human peripheral nerves, we compared the effectiveness of fibrin glue with neurorrhaphy for nerve gap restoration. METHODS: In twenty-four male Wistar rats, a fifteen mm defect in one sciatic nerve only was made and immediately repaired with an inverted polarity autograft. According to the used technique, rats were divided into Group A (Control), using traditional neurorrhaphy, and Group B (Study), using fibrine glue sealing; in total, 50% of rats were sacrificed at 16 weeks and 50% at 21 weeks. Before sacrifice, an assessment of motor function was done through Walking Track Analysis and an electroneurophysiological evaluation. After sacrifice, selected muscle mass indexes and the histology of the regenerated nerves were assessed. All data were evaluated by Student's t test for unpaired data. RESULTS: No significant differences were found between the two groups, with only the exception of a relative improvement in the tibialis anterior muscle's number of motor units in the study group. CONCLUSION: Despite the fact that the use of fibrin glue as a nerve sealant is not superior in terms of functional recovery, its effectiveness is comparable to that of microsurgical repair. Hence, the faster and technically easier glueing technique could deserve broader clinical application.

Clinical study of a micro-implantable pulse generator for the treatment of peripheral neuropathic pain: 3-month and 6-month results from the COMFORT-randomised controlled trial.

BACKGROUND: We report the results from the first large, postmarket, multicentre, randomised controlled trial (RCT) evaluating peripheral nerve stimulation (PNS) for the treatment of chronic peripheral pain with a micro-implantable pulse generator (micro-IPG). METHODS: Subjects meeting eligibility were randomised (2:1) to either the active arm receiving PNS and conventional medical management (CMM) or the control arm receiving CMM alone. Treatments were limited to the following areas: lower back, shoulder, knee and foot/ankle. RESULTS: At 6 months, the active arm achieved an 88% responder rate with a 70% average reduction in pain. At the 3-month primary endpoint, the active arm achieved an 84% responder rate with an average pain reduction of 67% compared with the control arm, which achieved a 3% responder rate with an average pain reduction of 6%. Both responder rate and pain reduction in the active arm were significantly better than in the control arm (p<0.001). A majority of patient-reported outcomes also reached statistical significance. There have been no reports of pocket pain and no serious adverse device effects. 81% of subjects found the external wearable component of the PNS system to be comfortable. CONCLUSIONS: This study successfully reached its primary endpoint-the active arm achieved a statistically significant superior responder rate as compared with the control arm at 3 months. These RCT results demonstrated that PNS, with this micro-IPG, is efficacious and safe. This ongoing study will follow subjects for 3 years, the results of which will be reported as they become available.

Radiolucent cerclage for humerus fractures: beware of radial nerve injury-a case report.

A 73-year-old woman was referred to a National Centre for Peripheral Nerve Injury with a post-operative left radial nerve degenerative lesion following open reduction and internal fixation of a proximal third humerus fracture using radiolucent Arthrex FiberTape® Cerclage as an adjunct to plating to improve stability. Intra-operative photographs illustrate compression of the radial nerve under the cerclage construct. Use of radiolucent cerclage for humerus fractures is increasing with modern systems capable of withstanding an ultimate load of 4300 N. We highlight the risk of debilitating neurological injury when not deployed safely and describe anatomical high-risk zones for injury. We emphasize the impact of delay in diagnosis and treatment.

Photobiomodulation as a Potential Therapy for Erectile Function: A Preclinical Study in a Cavernous Nerve Injury Model.

PURPOSE: To identify the optimal photobiomodulation (PBM) parameters using molecular, histological, and erectile function analysis in cavernous nerve injury. MATERIALS AND METHODS: A cavernous nerve injury was induced in 8-week-old C57BL/6J male mice that were subsequently divided randomly into age-matched control groups. Erectile function tests, penile histology, and Western blotting were performed 2 weeks after surgery and PBM treatment. RESULTS: The PBM treatment was administered for five consecutive days with a light-emitted diode (LED) device that delivers 660 nm±3% RED light, and near infra-red 830 nm±2% promptly administered following nerve-crushing surgery and achieved a notable restoration of erectile function approximately 90% of the control values. Subsequent in-vitro and ex-vivo analyses revealed the regeneration of neurovascular connections in both the dorsal root ganglion and major pelvic ganglion, characterized by the sprouting of neurites. Furthermore, the expression levels of neurotrophic, survival, and angiogenic factors exhibited a substantial increase across all groups subjected to PBM treatment. CONCLUSIONS: The utilization of PBM employing LED with 660 nm, 830 nm, and combination of both these wavelengths, exhibited significant efficacy to restore erectile function in a murine model of cavernous nerve injury. Thus, the PBM emerges as a potent therapeutic modality with notable advantages such as efficacy, noninvasiveness, and non-pharmacological interventions for erectile dysfunction caused by nerve injury.

Exploring an innovative decellularization protocol for porcine nerve grafts: a translational approach to peripheral nerve repair.

Introduction: Peripheral nerves are frequently affected by lesions caused by traumatic or iatrogenic damages, resulting in loss of motor and sensory function, crucial in orthopedic outcomes and with a significant impact on patients' quality of life. Many strategies have been proposed over years to repair nerve injuries with substance loss, to achieve musculoskeletal reinnervation and functional recovery. Allograft have been tested as an alternative to the gold standard, the autograft technique, but nerves from donors frequently cause immunogenic response. For this reason, several studies are focusing to find the best way to decellularize nerves preserving either the extracellular matrix, either the basal lamina, as the key elements used by Schwann cells and axons during the regenerative process. Methods: This study focuses on a novel decellularization protocol for porcine nerves, aimed at reducing immunogenicity while preserving essential elements like the extracellular matrix and basal lamina, vital for nerve regeneration. To investigate the efficacy of the decellularization protocol to remove immunogenic cellular components of the nerve tissue and to preserve the basal lamina and extracellular matrix, morphological analysis was performed through Masson's Trichrome staining, immunofluorescence, high resolution light microscopy and transmission electron microscopy. Decellularized porcine nerve graft were then employed in vivo to repair a rat median nerve lesion. Morphological analysis was also used to study the ability of the porcine decellularized graft to support the nerve regeneration. Results and Discussion: The decellularization method was effective in preparing porcine superficial peroneal nerves for grafting as evidenced by the removal of immunogenic components and preservation of the ECM. Morphological analysis demonstrated that four weeks after injury, regenerating fibers colonized the graft suggesting a promising use to repair severe nerve lesions. The idea of using a porcine nerve graft arises from a translational perspective. This approach offers a promising direction in the orthopedic field for nerve repair, especially in severe cases where conventional methods are limited.

Enhancing nerve regeneration in infraorbital nerve injury rat model: effects of vitamin B complex and photobiomodulation.

Orofacial nerve injuries may result in temporary or long-term loss of sensory function and decreased quality of life in patients. B vitamins are required for DNA synthesis and the repair and maintenance of phospholipids. In particular, vitamins B1, B6, and B12 are essential for neuronal function. Deficiency in vitamin B complex (VBC) has been linked to increased oxidative stress, inflammation and demyelination. Photobiomodulation (PBM) has antioxidant activity and is neuroprotective. In addition, a growing literature attests to the positive effects of PBM on nerve repair. To assess the effect of PBM and VBC on regenerative process we evaluated the expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), myelin basic protein (MBP), laminin and neurofilaments (NFs) using Western blotting to identify regenerative pattern after chronic constriction injury of the infraorbital nerve (CCI IoN) treated by PBM, VBC or its combination. After CCI IoN, the rats were divided into six groups naive, sham, injured (CCI IoN), treated with photobiomodulation (904 nm, 6.23 J/cm2, CCI IoN + PBM), treated with VBC (containing B1, B6 and B12) 5 times, CCI IoN + VBC) and treated with PBM and VBC (CCI IoN + VBC + PBM). The treatments could revert low expression of BDNF, MBP and laminin. Also reverted the higher expression of neurofilaments and enhanced expression of NGF. PBM and VBC could accelerate injured infraorbital nerve repair in rats through reducing the expression of neurofilaments, increasing the expression of BDNF, laminin and MBP and overexpressing NGF. These data support the notion that the use of PBM and VBC may help in the treatment of nerve injuries. This finding has potential clinical applications.

Advancements in autologous peripheral nerve transplantation care: a review of strategies and practices to facilitate recovery.

Autologous peripheral nerve transplantation, a pioneering technique in nerve injury treatment, has demonstrated remarkable progress. We examine recent nursing strategies and methodologies tailored to various anatomical sites, highlighting their role in postoperative recovery enhancement. Encompassing brachial plexus, upper limb, and lower limb nerve transplantation care, this discussion underscores the importance of personalized rehabilitation plans, interdisciplinary collaboration, and innovative approaches like nerve electrical stimulation and nerve growth factor therapy. Moreover, the exploration extends to effective complication management and prevention strategies, encompassing infection control and pain management. Ultimately, the review concludes by emphasizing the advances achieved in autologous peripheral nerve transplantation care, showcasing the potential to optimize postoperative recovery through tailored and advanced practices.

Shedding Light on Perioperative Nerve Injury: An Investigation Using the SHED (Symptoms Categorization-History Taking-Examination-Diagnostic Evaluations) Approach.

Peripheral nerve blocks (PNBs) provide analgesia and anesthesia in diverse surgical procedures. Despite their recognized benefits, the occurrence of complications, particularly peripheral nerve injuries (PNIs), is a noteworthy concern. Prompt identification and intervention for perioperative nerve injuries are crucial to prevent permanent neurological impairment. A meticulous, systematic evaluation centered on the onset and progression of symptoms becomes imperative. The SHED (symptoms categorization-history taking-examination-diagnostic evaluations) approach serves as a valuable tool for diagnosing causative factors, determining the type of nerve injury, and formulating an effective treatment plan to mitigate further harm. This case report employs the SHED approach to elucidate a perplexing instance of PNIs. The patient, experiencing neurological symptoms post-forearm surgery under a PNB, serves as a focal point. The report underscores the significance of a systematic, stepwise approach in managing patients with suspected PNIs. Vigilant patient monitoring, collaborative teamwork, shared responsibilities, and consideration of potential contributing factors beyond the nerve block are highlighted for an accurate diagnosis and effective treatment of PNIs. The aim is to guide healthcare professionals in navigating similar clinical scenarios, ultimately ensuring patient safety and optimizing outcomes.

Adjunctive Effect of Photobiomodulation Therapy with Nd:YAG Laser in the Treatment of Inferior Alveolar Nerve Paresthesia.

Background: Disruption of peripheral branches of the trigeminal nerve in the field of maxillofacial surgery is a known risk due to the close connection of these branches with the bony structures of the maxilla and mandible. As a result, injuries of the lingual nerve and inferior alveolar nerve take place within routine maxillofacial surgery procedures, including local anesthetic injection, wisdom tooth surgery, and dental implant placement, resulting in paresthesia and dysesthesia. During the last three decades, low-level lasers (LLL) have been frequently used in various medical fields. Lately, this application has increased in several sectors. Methods and materials: This experiment was designed to explore the effect of low-level laser therapy (LLLT) with Nd:YAG on the paresthesia and dysesthesia of the lower lip. This ethics committee of Tbzmed, Tabriz, Iran, proved the present experiment with ethical code: IR.TBZMED.REC.1401.839. Results: After completing 10 sessions of laser therapy for the case group consisting of 25 patients with lower lip anesthesia, the visual analog scale index results revealed that following six sessions of laser therapy, a significant difference appeared in contrast to the control group. Also, according to the two-point tests, significant difference among the experimental and the control group appeared after ninth session of the laser therapy. Conclusions: Altogether, these data suggested LLLT with Nd:YAG as an effective treatment option for decreasing the anesthesia of the lower lip.

No evidence of fascicular injury following a low-volume intraneural injection of the median nerve: a cadaveric study.

BACKGROUND: The test dose or hydrolocation technique allows rapid detection of spread location. Though its primary aim is to enhance safety in peripheral nerve blocks, evidence on the potential risks of an intraneural test aliquot is lacking. We conducted a cadaveric study to evaluate the risk of fascicular injury following a low-volume (<1 mL) intraneural injection of the median nerve. METHODS: Ten upper limbs from fresh unembalmed human cadavers were studied. In-plane ultrasound-guided intraneural injections of the median nerve were performed at mid, proximal, and distal locations using 1 mL of methylene blue and heparinized blood solution. Nerves were extracted and samples immersed in 10% buffered formalin for 4 weeks. Perpendicular 3 mm slices were obtained for H&E staining and light microscopy analysis. Our main objective was to assess the number of injured fascicles. Secondarily, we evaluated the pattern of intraneural spread. Fascicular injury was defined as the presence perineurium or axonal disruption and/or the presence of erythrocytes inside a nerve fascicle. RESULTS: Thirty injections were performed in 10 median nerves. Sonographic swelling was confirmed in 100% of the cases. 352 histological sections were analyzed to assess study outcomes. The mean number of fascicles on each section of median nerve was 20±6 covering 49%±7% of the nerve area. No evidence of axonal disruption nor intra-fascicular erythrocytes was found in any of the analyzed sections. CONCLUSIONS: Low-volume intraneural injections do not result in evident fascicular injury. Our findings support the use of a test dose in ultrasound-guided regional anesthesia.

Application of Adipose Stem Cells in 3D Nerve Guidance Conduit Prevents Muscle Atrophy and Improves Distal Muscle Compliance in a Peripheral Nerve Regeneration Model.

BACKGROUND: Peripheral nerve injuries (PNIs) represent a significant clinical problem, and standard approaches to nerve repair have limitations. Recent breakthroughs in 3D printing and stem cell technologies offer a promising solution for nerve regeneration. The main purpose of this study was to examine the biomechanical characteristics in muscle tissue distal to a nerve defect in a murine model of peripheral nerve regeneration from physiological stress to failure. METHODS: In this experimental study, we enrolled 18 Wistar rats in which we created a 10 mm sciatic nerve defect. Furthermore, we divided them into three groups as follows: in Group 1, we used 3D nerve guidance conduits (NGCs) and adipose stem cells (ASCs) in seven rats; in Group 2, we used only 3D NGCs for seven rats; and in Group 3, we created only the defect in four rats. We monitored the degree of atrophy at 4, 8, and 12 weeks by measuring the diameter of the tibialis anterior (TA) muscle. At the end of 12 weeks, we took the TA muscle and analyzed it uniaxially at 10% stretch until failure. RESULTS: In the group of animals with 3D NGCs and ASCs, we recorded the lowest degree of atrophy at 4 weeks, 8 weeks, and 12 weeks after nerve reconstruction. At 10% stretch, the control group had the highest Cauchy stress values compared to the 3D NGC group (0.164 MPa vs. 0.141 MPa, p = 0.007) and the 3D NGC + ASC group (0.164 MPa vs. 0.123 MPa, p = 0.007). In addition, we found that the control group (1.763 MPa) had the highest TA muscle stiffness, followed by the 3D NGC group (1.412 MPa), with the best muscle elasticity showing in the group in which we used 3D NGC + ASC (1.147 MPa). At failure, TA muscle samples from the 3D NGC + ASC group demonstrated better compliance and a higher degree of elasticity compared to the other two groups (p = 0.002 and p = 0.008). CONCLUSIONS: Our study demonstrates that the combination of 3D NGC and ASC increases the process of nerve regeneration and significantly improves the compliance and mechanical characteristics of muscle tissue distal to the injury site in a PNI murine model.

Physical exercise to promote regeneration after peripheral nerve injury in animal models: A systematic review.

Peripheral nerve injuries are common injuries that often have a drastic effect on patient's activities of daily living and physical function. While techniques for the surgical repair of these injuries have improved over time, rehabilitation methods following these repairs have been non-standardized and under researched. Electronic searches were conducted in Ovid/Medline and SCOPUS to identify articles that discuss rehabilitation and exercise following peripheral nerve injury in animal models and its effects on peripheral nerve regeneration and recovery of function. Thirty-eight articles met inclusion criteria; all were prospective studies in animal models. This systematic review suggests that exercise is a useful tool in returning autonomy to the individual and has beneficial effects in the recovery from peripheral nerve injury. It is beneficial to use rehabilitation exercises following the repair of peripheral nerve injuries to promote regeneration, and timing of that exercise may be just as important as the exercise prescribed. However, further studies with standardized models and outcome measures need to be conducted before translation to clinical trials.