Carvacrol presynaptically enhances spontaneous excitatory transmission and produces outward current in adult rat spinal substantia gelatinosa neurons

• We examined carvacrol actions in rat spinal substantia gelatinosa neurons.
• Carvacrol activated TRPA1 channels, resulting in glutamate release enhancement.
• We demonstrated for the first time that carvacrol activates central TRPA1 channels.
• Carvacrol also produced outward current by activating K+ channels. This action could contribute to the antinociceptive action of carvacrol.

Carvacrol, which is abundantly contained in oregano essential oils, has various pharmacological actions including antinociception. Although the oral administration of carvacrol results in antinociception, cellular mechanisms for this action have not been examined yet. We investigated the action of carvacrol on glutamatergic spontaneous excitatory transmission in substantia gelatinosa neurons which play a pivotal role in regulating nociceptive transmission from the periphery by using the patch-clamp technique in adult rat spinal cord slices. Carvacrol superfused for 2 min produced either spontaneous excitatory postsynaptic current frequency increase or outward current at −70 mV, or both of them in many of the neurons tested. The frequency increase and outward current had the EC50 values of 0.69 mM and 0.55 mM, respectively. The former action was inhibited by a selective TRPA1 antagonist HC-030031 but not a selective TRPV1 antagonist capsazepine, while the latter action was unaffected by their antagonists. The current–voltage relationship for the outward current indicated an involvement in the current of a change in the membrane permeability of K+ and its outward rectification. The outward current was inhibited in 10 mM-K+ but not K+-channel blockers [tetraethylammonium and Ba2+]-containing and 11.0 mM-Cl- Krebs solution. These results indicate that carvacrol increases the spontaneous release of l-glutamate from nerve terminals by activating TRPA1 but not TRPV1 channels and produces membrane hyperpolarization, which is possibly mediated by tetraethylammonium- and Ba2+-insensitive K+ channels, in substantia gelatinosa neurons. It is suggested that the hyperpolarizing effect of carvacrol could contribute to its antinociceptive action.