title: Antinociceptive Effects of Transcytosed Botulinum Neurotoxin Type A on Trigeminal Nociception in Rats.
abstract: We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions.
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
authors.forename: Geun-Woo
authors.initials: GW
authors.lastname: Lee
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
authors.forename: Kui-Ye
authors.initials: KY
authors.lastname: Yang
authors.affiliation: Department of Orofacial Pain and Oral Medicine, School of Dentistry, Yonsei University, Seoul 110-749, Korea.
authors.forename: Seong-Taek
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Department of Oral Anatomy, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
authors.forename: Yong-Cheol
authors.initials: YC
authors.lastname: Bae
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
authors.forename: Dong-Kuk
authors.initials: DK
authors.lastname: Ahn
keywords: BoNT-A; NMDA; Pain; Transcytosed; Trigeminal