Presynaptic enhancement by eugenol of spontaneous excitatory transmission in rat spinal substantia gelatinosa neurons is mediated by transient receptor potential A1 channels

Eugenol, which is contained in several plants including clove, has been widely used as an analgesic and anti-inflammatory drug in the dental clinic. Eugenol also has anesthetic effects and produces sedation and the reduction of convulsion threshold. These benefits have been partly attributed to the effects of eugenol on neural tissues, such as inhibition of voltage-gated ion channels. As expected from the fact that eugenol is a vanilloid compound, this drug activates transient receptor potential (TRP) V1 channels in the peripheral nervous system (PNS). Although eugenol affects synaptic transmission in the central nervous system (CNS), this has not yet been fully examined. We investigated how eugenol affects spontaneous glutamatergic excitatory transmission in substantia gelatinosa (SG; lamina II of Rexed) neurons of adult rat spinal cord slices by use of the blind whole-cell patch-clamp technique. Bath-applied eugenol reversibly enhanced spontaneous excitatory transmission and produced an outward current at −70 mV in SG neurons. The former action was due to a large increase in the frequency of spontaneous excitatory postsynaptic current (sEPSC) with a small increase in the amplitude. These actions of eugenol were seen by its repeated application and resistant to a voltage-gated Na+ channel blocker tetrodotoxin. The effect of eugenol on sEPSC frequency was concentration-dependent with an EC50 value of 3.8 mM and unaffected by a TRPV1 antagonist capsazepine, whereas inhibited by a nonspecific TRP antagonist ruthenium red and a TRPA1 antagonist HC-030031. On the other hand, the eugenol-induced outward current was not affected by these TRP antagonists. It is concluded that eugenol activates TRPA1 channels in the SG, leading to an increase in the spontaneous release of l-glutamate to SG neurons, and that eugenol also produces a membrane hyperpolarization that is not mediated by TRP channels. Eugenol is suggested to activate different types of TRP channel between the PNS and CNS.

▶Eugenol enhanced glutamate release to spinal dorsal horn neurons by TRPA1 activation. ▶This is so, although eugenol is a vanilloid compound. ▶Eugenol was suggested to act on different types of TRP between PNS and CNS. ▶This is the first study showing eugenol-induced excitatory transmission enhancement.