Analgesic effects of linalyl acetate via nociceptive TRPV1 inhibition in mice

Transient receptor potential vanilloid 1 (TRPV1) is primarily expressed in sensory neurons and functions as a nociceptive channel. TRPV1 is activated by capsaicin, acidic pH, and noxious heat. Compounds inhibiting TRPV1 have been explored to develop analgesic drugs. In this study, the effect of linalyl acetate (LA), a lavender essential oil component that exerts analgesic effects, on TRPV1 was investigated by measuring intracellular Ca2+ concentration ([Ca2+]i) and whole-cell membrane currents. The analgesic effects of LA on TRPV1-mediated pain were also examined. LA inhibited [Ca2+]i responses to capsaicin, acidic pH, and heat in mouse sensory neurons. Unlike the transient LA-inhibition on capsaicin- and heat-responses, its inhibition on acid-responses persisted even after the LA removal. In TRPV1-expressing HEK293 cells, LA reversibly suppressed [Ca2+]i responses to capsaicin and heat, but persistently inhibited those to acids. Similarly, LA reversibly attenuated current responses to capsaicin but durably suppressed those to acids. LA sustainingly inhibited the responses to spermine, an endogenous TRPV1 agonist, and reduced pain-related behaviors induced by spermine and noxious heat. These results indicate that LA inhibits TRPV1 in a mode-independent manner, with long-lasting inhibition of acid-induced TRPV1 activation. These inhibitory actions of LA on TRPV1 may be related to its analgesic effects.