Moieties of plant-derived compounds responsible for outward current production and TRPA1 activation in rat spinal substantia gelatinosa.

Abstract

Transient receptor potential ankyrin-1 (TRPA1) channels expressed in the central terminal of dorsal root ganglion neurons in the spinal substantia gelatinosa (SG) play a role in modulating nociceptive transmission. Although plant-derived compounds exhibiting antinociception (such as eugenol, carvacrol and thymol) activate TRPA1 channels to enhance spontaneous excitatory transmission while hyperpolarizing membranes in SG neurons without TRPA1 activation, specific chemical moieties involved in synaptic modulation are unknown. We examined the effects of other plant-derived compounds (guaiacol, vanillin, vanillic acid and p-cymene) on holding current and spontaneous excitatory transmission at -70 mV by applying the whole-cell patch-clamp technique to SG neurons in adult rat spinal cord slices. None of the compounds affected the frequency or amplitude of spontaneous excitatory postsynaptic current. Guaiacol and vanillic acid had no effect on holding currents, while vanillin and p-cymene produced an inward and outward current, respectively, in some neurons tested. Synaptic modulation was also observed within the same neuron as the activities of eugenol, carvacrol, thymol, and the chemically-related plant-derived compound zingerone occurred. A substituted group in eugenol and zingerone, but not in guaiacol, vanillin or vanillic acid, as well as an OH bound to the benzene ring of carvacrol and thymol, but not p-cymene, play a role in producing outward current and TRPA1 activation. Thus, the binding of such chemical moeties to the benzene ring of plant-derived compounds appears necessary to modulate nociceptive transmission in the SG. This information provides insight for the development of new analgesics based on plant-derived compounds.