Facilitatory effect of eugenol on excitatory synaptic transmission in rat spinal substantia gelatinosa neurons

Abstract

Eugenol (4-allyl-2-methoxyphenol), which is contained in several plants including clove and bay leaves, has been widely used as an analgesic and anti-inflammatory drug in the dental clinic. Furthermore, eugenol has a general anesthetic effect, and produces sedation and the reduction of convulsion threshold. These benefits have been partly attributed to the effects of eugenol on neural tissues. Eugenol depresses the conduction of action potential in nerve fibers and thus serves as a local anesthetic. Voltage-gated Na+, Ca2+ and K+ channels are inhibited by eugenol in rat trigeminal ganglion neurons or dorsal root ganglion (DRG) neurons. As expected from the fact that eugenol and capsaicin share the vanilloid moiety in chemical structure, eugenol activates transient receptor potential (TRP) V1 channels, nonselective cation channels, in rat DRG neurons. Although eugenol is suggested to affect synaptic transmission in the central nervous system, to our knowledge, this has not yet been fully examined. The present study investigated how eugenol affects glutamatergic spontaneous 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 in SG neurons in a concentration-dependent manner in a range of 1 - 5mM. This action was due to a large increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) with a small increase in the amplitude. Eugenol also produced an outward current at - 70mV. These actions of eugenol were seen by its repeated application and resistant to a voltage-gated Na+-channel blocker tetrodotoxin (0.5 mu M). The effect of eugenol (5mM) on sEPSC frequency was unaffected by a TRPV1 channel antagonist capsazepine (10 mu M) while inhibited by a non selective TRP channel antagonist ruthenium red (300 mu M). On the other hand, the eugenol-induced outward current was not affected by both of the antagonists. It is concluded that eugenol activates TRP channels other than TRPV1 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 hyper polarization which is not mediated by TRP channels. The former action could be involved in producing nociception.