Potential anti-nociceptive effect of beta-ionone on orofacial pain through GABA and glycine mimetic action on substantia gelatinosa neurons of trigeminal subnucleus caudalis in mice

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) plays a crucial role in integrating and regulating nociceptive inputs related to orofacial region. Although beta-ionone has been identified for its biomedical properties, its nociceptive effect was not fully studied. This study employed a whole-cell patch-clamp technique in juvenile mice to investigate the direct membrane effects of beta-ionone on SG neurons of the Vc. In a high chloride pipette solution, beta-ionone induced consistent inward currents which were unaffected in the presence of tetrodotoxin, CNQX and AP5 but declined in the presence of strychnine and picrotoxin. Beta-ionone also demonstrated the ability to increase the effect of glycine and GABA and decrease the spontaneous neuronal activities of SG neurons of the Vc. Electrophysiological findings suggest the antinociceptive effect of beta-ionone via GABA-, glycine-mimetic action on SG neurons. Formalin-induced orofacial pain model in mice was subsequently performed, which showed beta-ionone's significant dose-dependent antinociceptive effects during both phase 1 and 2. In summary, our results suggest the possible anti-nociceptive effect of beta-ionone through glycine and GABA mimetic actions on SG neuron of the Vc in mice, indicating its potential as a target for modulating orofacial pain.