Antinociceptive Effects of Botulinum Toxin Type A on Trigeminal Neuropathic Pain

Previous studies have demonstrated that botulinum toxin type a (bont-a) attenuates orofacial nociception. however,there has been no evidence of the participation of the voltage-gated sodium channels (navs) in the antinociceptive mechanisms of bont-a. this study investigated the cellular mechanisms underlying the antinociceptive effects of bont-a in a male sprague-dawley rat model of trigeminal neuropathic pain produced by malpositioned dental implants. the left mandibular second molar was extracted under anesthesia,followed by a miniature dental implant placement to induce injury to the inferior alveolar nerve. mechanical allodynia was monitored after subcutaneous injection of bont-a at 3,7,or 12 d after malpositioned dental implant surgery. subcutaneous injections of 1 or 3 u/kg of bont-a on postoperative day 3 significantly attenuated mechanical allodynia,although 0.3 u/kg of bont-a did not affect the air-puff threshold. a single injection of 3 u/kg of bont-a produced prolonged antiallodynic effects over the entire experimental period. treatment with bont-a on postoperative days 7 and 12,when pain had already been established,also produced prolonged antiallodynic effects. double treatments with 1 u/kg of bont-a produced prolonged,more antiallodynic effects as compared with single treatments. subcutaneous administration of 3 u/kg of bont-a significantly inhibited the upregulation of nav isoform 1.7 (nav1.7) expression in the trigeminal ganglion in the nerve-injured animals. these results suggest that antinociceptive effects of bont-a are mediated by an inhibition of upregulated nav1.7 expression in the trigeminal ganglion. bont-a is therefore a potential new therapeutic agent for chronic pain control,including neuropathic pain. © international & american associations for dental research 2016.