Analgesic Effect of Perineural Injection of BoNT/A on Neuropathic Pain Induced by Chronic Constriction Injury of Sciatic Nerve in Rats

Abstract

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 in ammasome-related molecules in injured sciatic nerves were examined at 12 days after surgery.Moreover, C-ber evoked potential in spinal dorsal horn was recorded. The expression of SNAP-25, neuroin ammation and synaptic plasticity in spinal dorsal horn of each group was 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 signi cantly 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 mechanisms of perineural injection of BoNT/A may be related to the protective effect on myelin sheath by inhibiting NLRP3 in ammasome and promoting autophagy ow, while the central mechanisms may be associated with inhibition of neuroin ammation and synaptic plasticity in spinal dorsal horn due to its ability to inhibit 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 mechanisms.

Botulinum toxin type A ameliorates rat dorsal root ganglia neuron pyroptosis in postherpetic neuralgia by upregulating cathelicidin antimicrobial peptide to inhibit neutrophil elastase

“…Wu et al found that Clec7a knockdown can ameliorate NP in vivo and in vitro by targeting NLRP3 inflammasome-stimulated pyroptosis (Wu et al, 2022). In chronic constriction injury-induced NP rat models, BoNT/A functions as an NLRP3 inflammasome inhibitor that decreases NLRP3 inflammasome component expression and IL-18 level, thus exhibiting analgesic effect (He et al, 2023). In line with previous findings, we observed a reduction in NLRP3, Caspase-1, and GSDMD protein expression along with a decline of IL-1β and IL-18 production in vivo and in vitro, suggesting the inhibition of NLRP3 inflammasome-mediated pyroptosis in PHN.…”