Eugenol and carvacrol induce temporally desensitizing patterns of oral irritation and enhance innocuous warmth and noxious heat sensation on the tongue

Eugenol and carvacrol, from the spices clove and oregano, respectively, are agonists of TRPV3, which is implicated in transduction of warmth and possibly heat pain. We investigated the temporal dynamics of lingual irritation elicited by these agents, and their effects on innocuous warmth and heat pain, using a half-tongue method in human subjects. The irritant sensation elicited by both eugenol and carvacrol decreased across repeated applications at a 1-minute interstimulus interval (self-desensitization) which persisted for at least 10 minutes. Both agents also cross-desensitized capsaicin-evoked irritation. Eugenol and carvacrol significantly increased the magnitude of perceived innocuous warmth (44 C) for >10 minutes, and briefly (<5 minutes) enhanced heat pain elicited by a 49 C stimulus. Similar albeit weaker effects were observed when thermal stimuli were applied after the tongue had been desensitized by repeated application of eugenol or carvacrol, indicating that the effect is not due solely to summation of chemoirritant and thermal sensations. Neither chemical affected sensations of innocuous cool or cold pain. A separate group of subjects was asked to subdivide eugenol and carvacrol irritancy into subqualities, the most frequently reported being numbing and warmth, with brief burning, stinging/pricking, and tingle, confirming an earlier study. Eugenol, but not carvacrol, reduced detection of low-threshold mechanical stimuli. Eugenol and carvacrol enhancement of innocuous warmth may involve sensitization of thermal gating of TRPV3 expressed in peripheral warm fibers. The brief heat hyperalgesia following eugenol may involve a TRPV3-mediated enhancement of thermal gating of TRPV1 expressed in lingual polymodal nociceptors.