5-HT3a receptor contributes to neuropathic pain by regulating central sensitization in a rat with brachial plexus avulsion.

PURPOSE: As a frequently occurring complication resulting from brachial plexus avulsion (BPA), neuropathic pain significantly impacts the quality of life of patients and places a substantial burden on their families. Recent reports have suggested that the 5-HT3a receptor may play a role in the development and regulation of neuropathic pain. The current study aimed to explore the involvement of the 5-HT3a receptor in neuropathic pain resulting from BPA in rats. METHODS: A rat model of neuropathic pain was induced through brachial plexus avulsion (BPA). The pain thresholds of the rats were measured after BPA. The spinal dorsal horn (SDH) of rats was collected at day 14 after surgery, and the expression and distribution of the 5-HT3a receptor were analyzed using immunohistochemistry and western blotting. The expression levels of various factors related to central sensitization were measured by western blot, including c-Fos, GFAP, IBA-1, IL-1ß and TNF-α. The effects of 5-HT3a receptor antagonists on hyperalgesia were assessed through behavioral tests after intrathecal administration of ondansetron. Additionally, at 120 min postinjection, the SDH of rats was acquired, and the change of expression levels of protiens related to central sensitization were measured by western blot. RESULTS: BPA induced mechanical and cold hypersensitivity in rats. The 5-HT3a receptor was increased and mainly distributed on neurons and microglia in the SDH after BPA, and the level of central sensitization and expression of inflammatory factors, such as c-Fos, GFAP, IBA-1, IL-1ß and TNF-α, were also increased markedly. Ondansetron, which is a selective 5-HT3a receptor antagonist, reversed the behavioral changes caused by BPA. The antagonist also decreased the expression of central sensitization markers and inflammatory factors. CONCLUSION: The results suggested that the 5-HT3a receptor is involved in neuropathic pain by regulating central nervous system sensitization in a rat brachial plexus avulsion model. Targeting the 5-HT3a receptor may be a promising approach for treating neuropathic pain after brachial plexus avulsion.

A rat model of modified contralateral C7 transfer permitting ulnar nerve recovery.

BACKGROUND: Contralateral C7 transfer (cC7) is an important treatment for total brachial plexus avulsion (TBPA), which sacrifices the recovery of the ulnar nerve (UN). The present study aimed to introduce an animal model of modified cC7 that preserved the deep branch of ulnar nerve (dbUN) and verify its feasibility. METHODS: Anatomical study: Lengths, diameters, and axon counts of dbUN and anterior interosseous (AIN) branches in six rats were measured. In vivo surgery: 18 rats were divided into three groups. Group A: Traditional cC7. Group B: Modified cC7 finished in one stage. Group C: Modified cC7 and AIN branch anastomosed with dbUN one month after the first stage. Electrophysiological examinations, muscle wet weight, muscle cross-sectional areas, and nerve axon counts were evaluated six months postoperatively. RESULTS: Anatomical study: The distances from dbUN and AIN branches to the midpoint of the inner and outer epicondyles connection of the humerus, diameters, and axon numbers of dbUN and AIN branches were analyzed, then AIN terminal branch (tbAIN) was anastomosed with dbUN. In vivo surgery: The differences in median nerve fiber counts were not significant. There were more UN axons in group A than in groups B and C. In electrophysiological examinations, muscle wet weight and cross-sectional area of the flexor digitorum profundus showed no significant difference, but the second interosseus cross-sectional areas in groups B and C were significantly larger than in group A. CONCLUSIONS: This study established an animal model of preserving dbUN in cC7 and verified its feasibility. The possibility of restoring dbUN was established.

Modified contralateral C7 transfer to restore ulnar nerve function without sacrificing median nerve recovery: an experimental study.

Contralateral C7 (cC7) transfer is a technique used in patients with total brachial plexus avulsion. An ulnar nerve graft (UNG) is usually used, as intrinsic function is not expected to be restored due to length of reinnervation required. In this study, we attempted to improve intrinsic function recovery by preserving the deep branch of the ulnar nerve (dbUN) and reanimating it with the anterior interosseous nerve (AIN) after cC7 transfer. Fifty-four rats were divided into the following three groups: Group A, traditional cC7 transfer to the median nerve with a UNG; Group B, cC7 transfer preserving and repairing the dbUN with the terminal branch of the AIN; Group C, same as Group B; however, the dbUN was coapted after 1 month with the AIN. At 3, 6 and 9 months postoperatively, the results of electrodiagnostic and histomorphometric examinations of the interosseous muscle were significantly better in Groups B and C, without affecting AIN recovery. In conclusion, the modified cC7 transfer technique can potentially improve intrinsic function recovery without affecting median nerve recovery.

Why It Is Necessary to Use the Entire Root rather than Partial Root When Doing Contralateral C7 Nerve Transfer: Cortical Plasticity Also Matters besides the Amount of Nerve Fibers.

Previous studies suggested that the mode of donor transection is a critical factor affecting the efficacy of the contralateral C7 (CC7) nerve transfer. Nevertheless, the mechanism underlying this phenomenon remains elusive. The aim of this study was to investigate the relationship between the division modes of the CC7 nerve and cortical functional reorganization of Sprague-Dawley rats. We hypothesized that different methods of CC7 nerve transection might induce differences in cortical functional reorganization, thus resulting in differences in surgery efficacy. BDNF, TNF-α/IL-6, and miR-132/134 were selected as indicators of cortical functional reorganization. No significant differences in all these indicators were noted between the entire group and the entire root+posterior division group (P > 0.05). BDNF and miR-132/134 levels in the entire group and the entire root+posterior division group were significantly increased compared with their levels in the posterior group and the blank control group (P < 0.001). In all groups, BDNF, TNF-α/IL-6, and miR-132/134 levels in both hemispheres initially increased and subsequently decreased until week 40. In conclusion, this study provided the evidence of dynamic changes in BDNF, TNF-α/IL-6, and miR-132/134 in the cortex of rats after CC7 nerve transfer using different transecting modes, demonstrating that different CC7 nerve divisions might result in different surgical effects through modulation of cortical reorganization.

Comparison of neuropathic pain characteristics associated with total brachial plexus injury before and after surgical repair: A retrospective study.

OBJECTIVES: The goal of this study was to compare clinical characteristics of neuropathic pain associated with total brachial plexus injury before and after surgeries and to correlate possible contributing factors concerning to the pain prognosis. PATIENTS AND METHODS: Thirty patients with both total brachial plexus injury and neuropathic pain were included. Neuropathic pain was evaluated in terms of pain intensities, symptoms and regions. Pain intensities were evaluated by a visual analogue scale. The Neuropathic Pain Symptoms Inventory questionnaire and body maps were used to compare the pain symptoms and regions. Demographic data, injury and repair information were evaluated to analyze the possible factors influencing the prognosis. RESULTS: The average pain score of all participants was 7.13 ± 2.46 preoperatively and 5.40 ± 2.08 postoperatively. All patients were divided into Pain Relief Group and Pain Aggravation Group. Older age (p = 0.042), machine traction injury (p = 0.019)and nerve transplantation(p = 0.015) seemed to be related with pain aggravation. Paroxysmal pain was aggravated after surgical repairs (p = 0.041), while paresthesia/dysesthesia improved after surgery (p = 0.003). The permanent component of the pain (spontaneous pain) did not show any significant change (p = 0.584). Pain in C5 (p < 0.001) and C6 (p = 0.031) dermatomes got relieved after surgery. CONCLUSION: This study revealed the neuropathic pain of most patients with total brachial plexus injury was alleviated after neurosurgery, and the pain prognosis of different symptoms and regions varied after the nerve repair.