Antinociceptive Effects of Botulinum Toxin Type A on Trigeminal Neuropathic Pain

Abstract

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.

Botulinum toxin type A promotes microglial M2 polarization and suppresses chronic constriction injury-induced neuropathic pain through the P2X7 receptor

“…These findings confirmed the relief of NP by BTX-A. The analgesic effect of BTX-A in NP in the current study was supported by previous studies [16,17].…”

“…Botulinum toxin type A (BTX-A) is an exotoxin released by Gram-positive anaerobic Clostridium botulinum and has been widely used in the treatment of dystonia and in aesthetic field [14,15]. Clinical studies have confirmed that BTX-A can effectively relieve NP with mild adverse reactions [16,17]. However, the exact mechanism of BTX-A action in NP is still undefined.…”

Participation of central GABAAreceptors in the trigeminal processing of mechanical allodynia in rats

“…Withdrawal responses produced by ten successive trials of ramped air-puff pressure (4 seconds in duration, 10 second intervals) were examined as described previously [16171819]. The intensity of the air-puff pressure was controlled using a pneumatic pump (BH2 system, Harvard Apparatus).…”

Effect of therapeutic exercise on knee osteoarthritis after intra-articular injection of botulinum toxin type A, hyaluronate or saline: A randomized controlled trial

“…Increased c-Fos expression may indicate increased neuronal activation through harmful stimuli. In addition, data from other investigations showed that BoNT-A might have an anti-nociceptive effect by down-regulating the voltage-gated Na + -channel expression on the rat trigeminal neuralgia (30), or by reducing the peripheral release of neurotransmitters (substance P, CGRP) and pro-inflammatory cytokine IL-1β in rat temporomandibular arthritis (31). Based on this information, a possible explanation of paininhibition by BoNT-A is that it reduces the release of neurotransmitters, such as substance P and others, thus blocking the pain signal pathway.…”