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Original Article

Korean J Physiol Pharmacol 2018; 22(5): 539-546

Published online September 1, 2018 https://doi.org/10.4196/kjpp.2018.22.5.539

Copyright © The Korean Journal of Physiology & Pharmacology.

Botulinum toxin type A enhances the inhibitory spontaneous postsynaptic currents on the substantia gelatinosa neurons of the subnucleus caudalis in immature mice

Seon-Hui Jang1, Soo-Joung Park1, Chang-Jin Lee2, Dong-Kuk Ahn3,*, and Seong-Kyu Han1,*

1Department of Oral Physiology, School of Dentistry & Institute of Oral Bioscience, Chonbuk National University, Jeonju 54896, 2Research and Development Division, Hugel Inc., Chuncheon 24206, 3Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Botulinum toxin type A (BoNT/A) has been used therapeutically for various conditions including dystonia, cerebral palsy, wrinkle, hyperhidrosis and pain control. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) receive orofacial nociceptive information from primary afferents and transmit the information to higher brain center. Although many studies have shown the analgesic effects of BoNT/A, the effects of BoNT/A at the central nervous system and the action mechanism are not well understood. Therefore, the effects of BoNT/A on the spontaneous postsynaptic currents (sPSCs) in the SG neurons were investigated. In whole cell voltage clamp mode, the frequency of sPSCs was increased in 18 (37.5%) neurons, decreased in 5 (10.4%) neurons and not affected in 25 (52.1%) of 48 neurons tested by BoNT/A (3 nM). Similar proportions of frequency variation of sPSCs were observed in 1 and 10 nM BoNT/A and no significant differences were observed in the relative mean frequencies of sPSCs among 1-10 nM BoNT/A. BoNT/A-induced frequency increase of sPSCs was not affected by pretreated tetrodotoxin (0.5 μM). In addition, the frequency of sIPSCs in the presence of CNQX (10 μM) and AP5 (20 μM) was increased in 10 (53%) neurons, decreased in 1 (5%) neuron and not affected in 8 (42%) of 19 neurons tested by BoNT/A (3 nM). These results demonstrate that BoNT/A increases the frequency of sIPSCs on SG neurons of the Vc at least partly and can provide an evidence for rapid action of BoNT/A at the central nervous system.

Keywords: Botulinum toxin type A, Pain, Spontaneous postsynaptic current, Substantia gelatinosa, Whole-cell recoding