Antinociceptive Effects of Transcytosed Botulinum Neurotoxin Type A on Trigeminal Nociception in Rats.
10.4196/kjpp.2015.19.4.349
- Author:
Hye Jin KIM
1
;
Geun Woo LEE
;
Min Ji KIM
;
Kui Ye YANG
;
Seong Taek KIM
;
Yong Cheol BAE
;
Dong Kuk AHN
Author Information
1. Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea. dkahn@knu.ac.kr
- Publication Type:Original Article
- Keywords:
BoNT-A;
NMDA;
Pain;
Transcytosed;
Trigeminal
- MeSH:
Animals;
Chronic Pain;
Freund's Adjuvant;
Head;
Horns;
Humans;
Male;
N-Methylaspartate;
Neurons;
Nociception*;
Rats*;
Rats, Sprague-Dawley
- From:The Korean Journal of Physiology and Pharmacology
2015;19(4):349-355
- CountryRepublic of Korea
- Language:English
-
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.
