ABSTRACT
The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis(Vc) is the first relay site for the orofacial nociceptive inputs via the thin myelinatedAδ and unmyelinated C primary afferent fibers. Borneol, one of the valuable timehonoredherbal ingredients in traditional Chinese medicine, is a popular treatmentfor anxiety, anesthesia, and antinociception. However, to date, little is known asto how borneol acts on the SG neurons of the Vc. To close this gap, the whole-cellpatch-clamp technique was applied to elucidate the antinociceptive mechanismresponding for the actions of borneol on the SG neurons of the Vc in mice. In thevoltage-clamp mode, holding at –60 mV, the borneol-induced non-desensitizinginward currents were not affected by tetrodotoxin, a voltage-gated Na+ channelblocker, 6-cyano-7-nitro-quinoxaline-2,3-dione, a non-N-methyl-D-aspartate (NMDA)glutamate receptor antagonist and DL-2-amino-5-phosphonopentanoic acid, anNMDA receptor antagonist. However, borneol-induced inward currents were partiallydecreased in the presence of picrotoxin, a -aminobutyric acid (GABA)A receptorantagonist, or strychnine, a glycine receptor antagonist, and was almost suppressedin the presence of picrotoxin and strychnine. Though borneol did not show any effecton the glycine-induced inward currents, borneol enhanced GABA-mediatedresponses. Beside, borneol enhanced the GABA-induced hyperpolarization under thecurrent-clamp mode. Altogether, we suggest that borneol contributes in part towardmediating the inhibitory GABA and glycine transmission on the SG neurons of the Vcand may serve as an herbal therapeutic for orofacial pain ailments.
ABSTRACT
The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis(Vc) is the first relay site for the orofacial nociceptive inputs via the thin myelinatedAδ and unmyelinated C primary afferent fibers. Borneol, one of the valuable timehonoredherbal ingredients in traditional Chinese medicine, is a popular treatmentfor anxiety, anesthesia, and antinociception. However, to date, little is known asto how borneol acts on the SG neurons of the Vc. To close this gap, the whole-cellpatch-clamp technique was applied to elucidate the antinociceptive mechanismresponding for the actions of borneol on the SG neurons of the Vc in mice. In thevoltage-clamp mode, holding at –60 mV, the borneol-induced non-desensitizinginward currents were not affected by tetrodotoxin, a voltage-gated Na+ channelblocker, 6-cyano-7-nitro-quinoxaline-2,3-dione, a non-N-methyl-D-aspartate (NMDA)glutamate receptor antagonist and DL-2-amino-5-phosphonopentanoic acid, anNMDA receptor antagonist. However, borneol-induced inward currents were partiallydecreased in the presence of picrotoxin, a -aminobutyric acid (GABA)A receptorantagonist, or strychnine, a glycine receptor antagonist, and was almost suppressedin the presence of picrotoxin and strychnine. Though borneol did not show any effecton the glycine-induced inward currents, borneol enhanced GABA-mediatedresponses. Beside, borneol enhanced the GABA-induced hyperpolarization under thecurrent-clamp mode. Altogether, we suggest that borneol contributes in part towardmediating the inhibitory GABA and glycine transmission on the SG neurons of the Vcand may serve as an herbal therapeutic for orofacial pain ailments.
ABSTRACT
The lamina II, also called the substantia gelatinosa (SG), of the trigeminal subnucleus caudalis (Vc), is thought to play an essential role in the control of orofacial nociception. Glycine and serotonin (5-hydroxytryptamine, 5-HT) are the important neurotransmitters that have the individual parts on the modulation of nociceptive transmission. However, the electrophysiological effects of 5-HT on the glycine receptors on SG neurons of the Vc have not been well studied yet. For this reason, we applied the whole-cell patch clamp technique to explore the interaction of intracellular signal transduction between 5-HT and the glycine receptors on SG neurons of the Vc in mice. In nine of 13 neurons tested (69.2%), pretreatment with 5-HT potentiated glycine-induced current (I(Gly)). Firstly, we examined with a 5-HT₁ receptor agonist (8-OH-DPAT, 5-HT(1/7) agonist, co-applied with SB-269970, 5-HT₇ antagonist) and antagonist (WAY-100635), but 5-HT₁ receptor agonist did not increase IGly and in the presence of 5-HT₁ antagonist, the potentiation of 5-HT on I(Gly) still happened. However, an agonist (α-methyl-5-HT) and antagonist (ketanserin) of the 5-HT₂ receptor mimicked and inhibited the enhancing effect of 5-HT on I(Gly) in the SG neurons, respectively. We also verified the role of the 5-HT₇ receptor by using a 5-HT₇ antagonist (SB-269970) but it also did not block the enhancement of 5-HT on I(Gly). Our study demonstrated that 5-HT facilitated I(Gly) in the SG neurons of the Vc through the 5-HT₂ receptor. The interaction between 5-HT and glycine appears to have a significant role in modulating the transmission of the nociceptive pathway.
Subject(s)
Animals , Mice , Glycine , Neurons , Neurotransmitter Agents , Nociception , Patch-Clamp Techniques , Receptors, Glycine , Serotonin , Signal Transduction , Substantia GelatinosaABSTRACT
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.