Inhibitory action of citronellol on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in juvenile mice

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) serves as the primary relay point for orofacial nociceptive inputs transmitted via thin myelinated Aδ and unmyelinated C primary afferent fibers. Citronellol is a monoterpenoid alcohol found in the essential oil of various medicinal plants, such as Cymbopogon citratus. It has been shown to be able to alleviate orofacial pain. However, the precise mechanism by which citronellol modulates SG neurons in the Vc remains unclear. To investigate this, the whole-cell patch-clamp technique was used to examine antinociceptive effects of citronellol on SG neurons in the Vc of mice. In a high-chloride pipette solution, citronellol consistently induced inward currents which persisted even in the presence of tetrodotoxin (a voltage-gated Na⁺ channel blocker), 6-cyano-7-nitroquinoxaline-2,3-dione (a non-N-methyl-d-aspartate glutamate receptor antagonist), and DL-2-amino-5-phosphonopentanoic acid (an N-methyl-d-aspartate receptor antagonist). Nevertheless, citronellol-induced inward currents were partially inhibited by picrotoxin, a GABA_A receptor antagonist, or strychnine, a glycine receptor antagonist. Citronellol-induced inward currents were almost fully blocked when both strychnine and picrotoxin were applied together. In addition, citronellol enhanced both GABA-induced inward currents and glycine-induced inward currents. These findings suggest that citronellol can mediate inhibitory effects of GABA and glycine on SG neurons in the Vc and serve as a potential herbal treatment for orofacial pain.