Effects Of Carvacrol On Glutamatergic Spontaneous Excitatory Transmission In Adult Rat Spinal Substantia Gelatinosa Neurons

Objective: Carvacrol, which is abundantly contained in oregano essential oils, hasvarious pharmacological actions including anticonvulsive and antinociceptive actions.Although the oral administration of carvacrol results in antinociception, cellularmechanisms for this action have not been examined yet. We examined the action ofcarvacrol on glutamatergic spontaneous excitatory transmission in the substantiagelatinosa (SG; lamina II of Rexed) neurons of spinal cord slices.Methods: Male adult Sprague-Dawley rats (6-8weeks old) were anesthetized withurethane (1.2g/kg, intraperitoneal), and then lumbosacral laminectomy wasperformed. The lumbosacral spinal cord (L1-S3) was removed and mounted on avibrating microslicer and then a600-800μm thick transverse slice was cut. The slicewas placed on nylon mesh in the recording chamber. The blind whole-cellpatch-clamp technique was applied to the SG neurons of the slices. Carvacrol andother drugs were applied by superfusion with a change in solutions in the recordingchamber.Results: Carvacrol superfused for2min produced either spontaneous excitatorypostsynaptic current (sEPSC) frequency increase or outward current at-70mV, orboth of them in many of the neurons tested. The frequency increase and outwardcurrent had the EC50values of0.69and0.55mM, respectively. The former actionwas inhibited by TRPA1antagonist HC-030031but not TRPV1antagonistcapsazepine, while the latter action was unaffected by their antagonists.Current-voltage relationship of the outward current indicated an involvement in thecurrent of change in membrane permeabilities of K+and other ions. The outwardcurrent was inhibited in10mM-K+but not K+-channel blockers [tetraethylammonium(TEA) and Ba2+]-containing Krebs solution.Conclusion: These results indicate that carvacrol increases the spontaneous releaseof L-glutamate from nerve terminals by activating TRPA1but not TRPV1channelsand produces membrane hyperpolarization, a part of which is mediated by TEA-andBa2+-insensitive K+channel, in SG neurons. It is suggested that the hyperpolarizing effect of carvacrol could contribute to its antinociceptive effect.