Antinociceptive Effects of Botulinum Toxin Type A on Trigeminal Neuropathic Pain

Ronald Dubner, K. Y. Yang, M. J. Kim, J. S. Ju, S. K. Park, C. G. Lee, S. T. Kim, Y. C. Bae, D. K. Ahn

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1183-1190
Number of pages8
JournalJournal of Dental Research
Volume95
Issue number10
DOIs
Publication statusPublished - 2016 Sep 1

Bibliographical note

Funding Information:
This research was supported by the National Research Foundation of Korea (funded by the Ministry of Science, ICT and Future Planning; 2008-0062282 and 2012M3A9B6055414) and by Hugel, Inc.

Publisher Copyright:
© International & American Associations for Dental Research 2016.

All Science Journal Classification (ASJC) codes

  • Dentistry(all)

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