Lingual heat and cold sensitivity following exposure to capsaicin or menthol.

Capsaicin and menthol are the most extensively studied of all chemesthetic agents. Capsaicin is best known as a nociceptive stimulus and menthol as an artificial cooling agent, but both have a combination of thermal and nociceptive properties. Capsaicin can affect perception of nonpainful warmth and heat as well as burning pain and menthol can induce burning and stinging as well as cold. However, few studies have investigated capsaicin’s effects on temperature perception (Green, 1986b) and only recently have psychophysical reports of irritation from menthol (Green, 1992; Dessirier et al., 2001) been substantiated by evidence that it stimulates nociceptors as well as low-threshold cold fibers (Okazawa et al., 2004; Wasner et al., 2004). The identification of separate transient receptor protein (TRP) gated channels sensitive to capsaicin and menthol has further increased interest in these chemicals. TRPV1 is sensitive to capsaicin, heat and protons (Caterina et al., 1999) and has been localized in taste papillae as well as other oral tissue (Ishida et al., 2002; Kido et al., 2003). TRPM8 is sensitive to menthol (McKemy et al., 2002; Peier et al., 2002) and is assumed to be the primary receptor for innocuous cold. However, its high threshold (<30°C) and recent evidence that it is sometimes co-expressed with TRPV1 (Okazawa et al., 2004) leaves open the possibility that TRPM8 is expressed on some nociceptors as well. Psychophysical studies of the effects of menthol and capsaicin on temperature perception have yielded a complicated array of interactions. In the first study of menthol’s oral thermal effects (Green, 1985), brief (5 s) exposures to L-menthol in water enhanced perceived warmth but failed to enhance perceived cold. However, pre-exposure to L-menthol not only led to the expected enhancement of cooling but also to a suppression of warmth. Two later studies replicated the suppressive effect of warmth on the lip (Green, 1986a) and forearm (Green, 1992). On the other hand, capsaicin has been shown to enhance warmth during transient oral exposures (Green, 1986b) and to suppress warmth following repeated applications to the skin that are sufficient to induce self-desensitization (Simone and Ochoa, 1991). What was unclear in all of these studies was whether the reduced heat perception from the two chemicals resulted from effects on warm receptors, nociceptors, or both.