title: 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.
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: K Y
authors.initials: KY
authors.lastname: Yang
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Ju
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: S K
authors.initials: SK
authors.lastname: Park
authors.affiliation: Research and Development Division, Hugel, Inc., Chuncheon, Korea.
authors.forename: C G
authors.initials: CG
authors.lastname: Lee
authors.affiliation: Department of Orofacial Pain and Oral Medicine, School of Dentistry, Yonsei University, Seoul, Korea.
authors.forename: S T
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Department of Oral Anatomy, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: Y C
authors.initials: YC
authors.lastname: Bae
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea dkahn@knu.ac.kr.
authors.forename: D K
authors.initials: DK
authors.lastname: Ahn
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D006930:Hyperalgesia; D007279:Injections, Subcutaneous; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014277:Trigeminal Neuralgia / Q000188:drug therapy*
chemical_list: D019274:Botulinum Toxins, Type A
keywords: allodynia; neuropathic pain; orofacial pain; trigeminal nerve; voltage dependent sodium channel