Background: Traumatic neuroma is a common sequela of peripheral nerve injury or amputation, which often leads to severe neuropathic pain. The present study investigated the effect of local lidocaine administration on preventing the formation of traumatic neuroma. Methods: Forty-eight male Sprague–Dawley rats were randomly assigned to two groups. The lidocaine group underwent sciatic nerve transection, followed by an injection of lidocaine (0.5%) around the proximal of a severed sciatic nerve under ultrasound-guidance 2–7 days after neurectomy. In the control group, rats received an injection of saline following neurectomy. The autotomy score, mechanical allodynia, thermal hyperalgesia, histological assessment, expression of neuroma, and pain-related markers were detected. Results: Lidocaine treatment reduced the autotomy score and attenuated mechanical allodynia and thermal hyperalgesia. The mRNA expression of α-SMA, NGF, TNF-α, and IL-1β all significantly decreased in the lidocaine group in comparison to those in the saline control group. The histological results showed nerve fibers, demyelination, and collagen hyperplasia in the proximal nerve stump in the saline control group, which were significantly inhibited in the lidocaine group. Conclusions: The present study demonstrated that local lidocaine administration could inhibit the formation of painful neuroma due to traumatic nerve injury. Full article

Critically sized nerve defects cause devastating life-long disabilities and require interposition for reconstruction. Additional local application of mesenchymal stem cells (MSCs) is considered promising to enhance peripheral nerve regeneration. To better understand the role of MSCs in peripheral nerve reconstruction, we performed a systematic review and meta-analysis of the effects of MSCs on critically sized segment nerve defects in preclinical studies. 5146 articles were screened following PRISMA guidelines using PubMed and Web of Science. A total of 27 preclinical studies (n = 722 rats) were included in the meta-analysis. The mean difference or the standardized mean difference with 95% confidence intervals for motor function, conduction velocity, and histomorphological parameters of nerve regeneration, as well as the degree of muscle atrophy, was compared in rats with critically sized defects and autologous nerve reconstruction treated with or without MSCs. The co-transplantation of MSCs increased the sciatic functional index (3.93, 95% CI 2.62 to 5.24, p < 0.00001) and nerve conduction velocity recovery (1.49, 95% CI 1.13 to 1.84, p = 0.009), decreased the atrophy of targeted muscles (gastrocnemius: 0.63, 95% CI 0.29 to 0.97 p = 0.004; triceps surae: 0.08, 95% CI 0.06 to 0.10 p = 0.71), and promoted the regeneration of injured axons (axon number: 1.10, 95% CI 0.78 to 1.42, p < 0.00001; myelin sheath thickness: 0.15, 95% CI 0.12 to 0.17, p = 0.28). Reconstruction of critically sized peripheral nerve defects is often hindered by impaired postoperative regeneration, especially in defects that require an autologous nerve graft. This meta-analysis indicates that additional application of MSC can enhance postoperative peripheral nerve regeneration in rats. Based on the promising results in vivo experiments, further studies are needed to demonstrate potential clinical benefits. Full article

Background: Nerve compression syndromes of the upper extremity are a common cause of neuropathic pain and functional impairment. Recently, platelet-rich plasma (PRP) infiltrations have emerged as an effective biological approach to the treatment of this type of injury. The objectives of this retrospective observational study were to assess clinical improvement in patients with median and ulnar nerve entrapment syndrome after undergoing biologically-assisted nerve release surgery with plasma-rich-in-growth-factors (PRGF) technology. Methods: Participants (n = 39) with moderate-to-severe nerve compression syndrome of the upper limb diagnosed by both electromyography and clinical examination, and who were treated with PRGF, were identified from the center’s medical records. The evaluation was based on patient-reported outcomes. Pre- and post-treatment differences in the Visual analog scale (VAS), the Boston carpal tunnel questionnaire (BCTQ), and the Quick-DASH score were assessed. Results: Three study groups were conducted: patients with carpal tunnel syndrome (n = 16), with recurrent carpal tunnel syndrome (n = 8), and with ulnar nerve entrapment (n = 15). The median follow-up was 12 months (interquartile range (IQR), 9–16). In comparison to pre-treatment values, all three study groups obtained statistically significant improvements for the three analyzed scales at the end of the follow-up, with p < 0.001 for all scales in the carpal tunnel syndrome and ulnar nerve entrapment groups and p < 0.01 for all scales in the recurrent carpal tunnel syndrome group. There were no serious adverse effects in the analyzed patients. Conclusion: PRGF-assisted open surgical nerve release treatment (intraneural and perineural liquid PRGF infiltrations and nerve wrapping with PRGF membrane) exerts long-term beneficial effects on pain reduction and functional improvement in the nerve and nerve–muscle unit in patients with upper extremity compression syndromes. Full article

Various methods have been used to improve function and manage facial nerve injury. Although electrical stimulation therapy is frequently used to treat facial paralysis, its effects have been found to vary and no clear standards have been developed. The current review describes the results of preclinical and clinical studies evaluating the effectiveness of electrical stimulation therapy in promoting the recovery of a peripheral facial nerve injury. Evidence is presented showing the efficacy of electrical stimulation in promoting nerve regeneration after peripheral nerve injuries in both animal models and human patients. The ability of electrical stimulation to promote the recovery of facial paralysis was found to depend on the type of injury (compression or transection), the species of animal tested, the type of disease, the frequency and method of electrical stimulation, and the duration of the follow-up. Electrical stimulation, however, can also have potential negative outcomes, such as reinforcing synkinesis, including mistargeted axonal regrowth via inappropriate routes; excessive collateral axonal branching at the lesion site; and multiple innervations at neuromuscular junctions. Because of the inconsistencies among studies and the low quality of evidence, electrical stimulation therapy is not currently regarded as a primary treatment of facial paralysis in patients. However, understanding the effects of electrical stimulation, as determined in preclinical and clinical studies, is important for the potential validity of future research on electrical stimulation. Full article

Peripheral nerve injuries requiring surgical repair affect over 100,000 individuals in the US annually. Three accepted methods of peripheral repair include end-to-end, end-to-side, and side-to-side neurorrhaphy, each with its own set of indications. While it remains important to understand the specific circumstances in which each method is employed, a deeper understanding of the molecular mechanisms underlying the repair can add to the surgeon’s decision-making algorithm when considering each technique, as well as help decide nuances in technique such as the need for making epineurial versus perineurial windows, length and dept of the nerve window, and distance from target muscle. In addition, a thorough knowledge of individual factors that are active in a particular repair can help guide research into adjunct therapies. This paper serves to summarize the similarities and divergences of the three commonly used nerve repair strategies and the scope of molecular mechanisms and signal transduction pathways in nerve regeneration as well as to identify the gaps in knowledge that should be addressed if we are to improve clinical outcomes in our patients. Full article