He Juan-Juan, Wei Xiao-Mei, Wu Meng-Li, Song Zu-Biao, Jiang Li, Zhang Wei-Xi
Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, Guangzhou, 510080, China.
Department of Rehabilitation, The Third Affiliated Hospital, Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, China.
Neurochem Res. 2023 Jul;48(7):2161-2174. doi: 10.1007/s11064-023-03893-0. Epub 2023 Feb 24.
This study was designed to investigate the analgesic effect of perineural injection of BoNT/A on neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) and possible mechanisms. SD rats were randomly divided into Sham group, CCI group and BoNT/A group. Paw mechanical withdrawal threshold (pMWT) and paw thermal withdrawal latency (pTWL) of each group were detected at different time points after surgery. The expression of myelin markers, autophagy markers and NLRP3 inflammasome-related molecules in injured sciatic nerves were examined at 12 days after surgery. Moreover, C-fiber evoked potential in spinal dorsal horn was recorded. The expression of SNAP-25, neuroinflammation and synaptic plasticity in spinal dorsal horn of each group were examined. Then rats treated with BoNT/A were randomly divided into DMSO group and Wnt agonist group to further explore the regulatory effect of BoNT/A on Wnt pathway. We found that pMWT and pTWL of ipsilateral paw were significantly decreased in CCI group compared with Sham group, which could be improved by perineural injection of BoNT/A at days 7, 9 and 12 after surgery. The peripheral analgesic mechanisms of perineural injection of BoNT/A might be related to the protective effect on myelin sheath by inhibiting NLRP3 inflammasome and promoting autophagy flow, while the central analgesic mechanisms might be associated with inhibition of neuroinflammation and synaptic plasticity in spinal dorsal horn due to inhibiting SNAP-25 and Wnt pathway. As a new route of administration, perineural injection of BoNT/A can relieve CCI induced neuropathic pain probably via both peripheral and central analgesic mechanisms.
本研究旨在探讨神经周围注射肉毒杆菌毒素A（BoNT/A）对坐骨神经慢性压迫损伤（CCI）诱导的神经性疼痛的镇痛作用及可能机制。将SD大鼠随机分为假手术组、CCI组和BoNT/A组。在术后不同时间点检测每组大鼠的爪部机械缩足阈值（pMWT）和爪部热缩足潜伏期（pTWL）。在术后12天检测损伤坐骨神经中髓鞘标志物、自噬标志物和NLRP3炎性小体相关分子的表达。此外，记录脊髓背角的C纤维诱发电位。检测每组大鼠脊髓背角中SNAP-25的表达、神经炎症和突触可塑性。然后将接受BoNT/A治疗的大鼠随机分为二甲基亚砜（DMSO）组和Wnt激动剂组，以进一步探讨BoNT/A对Wnt通路的调节作用。我们发现，与假手术组相比，CCI组同侧爪的pMWT和pTWL显著降低，术后第7、9和12天神经周围注射BoNT/A可改善这一情况。神经周围注射BoNT/A的外周镇痛机制可能与通过抑制NLRP3炎性小体和促进自噬流对髓鞘的保护作用有关，而中枢镇痛机制可能与抑制脊髓背角的神经炎症和突触可塑性有关，这是由于抑制了SNAP-25和Wnt通路。作为一种新的给药途径，神经周围注射BoNT/A可能通过外周和中枢镇痛机制缓解CCI诱导的神经性疼痛。
