Inhibitory actions of borneol on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice

Abstract

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is the first relay site for the orofacial nociceptive inputs via the thin myelinated Aδ and unmyelinated C primary afferent fibers. Borneol, one of the valuable timehonored herbal ingredients in traditional Chinese medicine, is a popular treatment for anxiety, anesthesia, and antinociception. However, to date, little is known as to how borneol acts on the SG neurons of the Vc. To close this gap, the whole-cell patch-clamp technique was applied to elucidate the antinociceptive mechanism responding for the actions of borneol on the SG neurons of the Vc in mice. In the voltage-clamp mode, holding at-60 mV, the borneol-induced non-desensitizing inward currents were not affected by tetrodotoxin, a voltage-gated Na + channel blocker, 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, an NMDA receptor antagonist. However, borneol-induced inward currents were partially decreased in the presence of picrotoxin, a -aminobutyric acid (GABA) A receptor antagonist, or strychnine, a glycine receptor antagonist, and was almost suppressed in the presence of picrotoxin and strychnine. Though borneol did not show any effect on the glycine-induced inward currents, borneol enhanced GABA-mediated responses. Beside, borneol enhanced the GABA-induced hyperpolarization under the current-clamp mode. Altogether, we suggest that borneol contributes in part toward mediating the inhibitory GABA and glycine transmission on the SG neurons of the Vc and may serve as an herbal therapeutic for orofacial pain ailments.

Naringenin modulates GABA mediated response in a sexdependent manner in substantia gelatinosa neurons of trigeminal subnucleus caudalis in immature mice

“…In addition, radioligand binding assay reveals that substances like (S) naringenin, glabrol, and 8-lavandulyl- flavanones act on the GABA receptors’ benzodiazepine site [ 50 ]. Besides flavonoid naringenin, essential oil linalool [ 51 ], terpene borneol [ 52 ], and biphenyl honokiol [ 53 ] possess the potential to influence the GABA receptor-mediated action on SG neurons of Vc. Notably, 6-hydroxyflavone, a flavone, shows diverse responses towards GABA, acting as a subtype-selective partial positive allosteric modulator at the flumazenil-sensitive benzodiazepine site and flumazenil-sensitive partial inverse agonist or negative modulator at α1β3γ2, α2β3γ2, and α5β3γ2 but not at α3β3γ2 receptor subunits [ 8 ].…”

Multiple regulation and targeting effects of borneol in the neurovascular unit in neurodegenerative diseases

“…It can also mediate the activation of GABA A and glycine receptors to induce repeatable inward currents on substantia gelatinosa neurons and directly acts on postsynaptic substantia gelatinosa neurons. 63 These indicate that borneol affects and protects neurons.…”

“…Borneol can inhibit the transmission of GABA and glycine in the substantia gelatinosa neurons of the trigeminal subnucleus caudalis. It can also mediate the activation of GABA A and glycine receptors to induce repeatable inward currents on substantia gelatinosa neurons and directly acts on postsynaptic substantia gelatinosa neurons 63 . These indicate that borneol affects and protects neurons.…”