Baicalin Activates Glycine and γ -Aminobutyric Acid Receptors on Substantia Gelatinosa Neurons of the Trigeminal Subsnucleus Caudalis in Juvenile Mice

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) receives nociceptive afferent inputs from thin-myelinated Afibers and unmyelinated C fibers and has been shown to be involved in the processing of orofacial nociceptive information. Scutellaria baicalensis Georgi (Huang-Qin, SbG), one of the 50 fundamental herbs of Chinese herbology, has been used historically as anti-inflammatory and antineoplastic medicine. Baicalin, one of the major compounds of SbG, has been reported to have neuroprotective, anti-inflammatory and analgesic effects. However, the receptor type activated by baicalin and its precise action mechanism on the SG neurons of Vc have not yet been studied. The whole-cell patch clamp technique was performed to examine the ion channels activated by baicalin on the SG neurons of Vc. In high Cl-pipette solution, the baicalin (300μM) induced repeatable inward currents (-24.8±3.57pA, n=19) without desensitization on all the SG neurons tested. Further, the inward currents showed a concentration (0.1-3mM) dependent pattern. The inward current was sustained in the presence of tetrodotoxin (0.5μM), a voltage sensitive Na+ channel blocker. In addition, baicalin-induced inward currents were reduced in the presence of picrotoxin (50μM), a GABA_A receptor antagonist, flumazenil (100μM), a benzodiazepine-sensitive GABA A receptor antagonist, and strychnine (2μM), a glycine receptor antagonist, respectively. These results indicate that baicalin has inhibitory effects on the SG neurons of the Vc, which are due to the activation of GABA A and/or the glycine receptor. Our results suggest that baicalin may be a potential target for orofacial pain modulation.