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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.

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) receives orofacial nociceptive information from primary afferent neurons and transmits this information to higher brain centers. Resveratrol (3, 5, 4′-trihydroxystilbene) is a polyphenolic compound found in various plant species and have been reported to have various biological activities, including analgesic effects. Although many studies have investigated the mechanism of action of resveratrol in terms of its antinociceptive effect, limited research has been conducted on the effects of resveratrol on SG neurons involved in orofacial pain transmission, especially to understand its relevance to glutamate receptors. To address this research gap, the present study investigated the effect of resveratrol on glutamate receptor activity in SG neurons using the whole-cell patch-clamp technique. The results showed that resveratrol significantly inhibited glutamate-mediated inward currents in SG neurons. Notably, there were no changes in α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid-or kainic acid-mediated inward currents in the presence of resveratrol, although N-methyl-D-aspartate (NMDA)-mediated inward currents were markedly suppressed. Taken together, these results suggest that resveratrol may be involved in orofacial pain transmission in SG neurons of the Vc by inhibiting the activity of NMDA receptors, among ionotropic glutamate receptors.