Different responses to repeated applications of zingerone in behavioral studies, recordings from intact and cultured TG neurons, and from VR1 receptors

When applied repetitively to the cornea, capsaicin, the pungent compound in hot pepper, causes an initial eye-wiping response that diminishes upon rep eated exposure (tachyphylaxis). This diminution, however, is not observed u pon repetitive application of its pungent analogue, zingerone, to the corne a or tongue. In addition, compared with capsaicin, the lingual application of zingerone produces a gustatory response with a shorter latency and durat ion. Because both the tongue and the cornea are innervated by the trigemina l nerve, and because zingerone and capsaicin are structurally related, it i s not evident why the responses to these compounds should give such differe nt behavioral and psychophysical endpoints. We have addressed this issue by measuring the neural responses from rat trigeminal ganglion neurons (TG) t o repeated applications of zingerone applied to the cornea, from cultured r at TG neurons, and from cloned capsaicin receptors (VR1) expressed in Xenop us oocytes and then comparing these effects to those evoked by capsaicin. E xtracellular recordings from the trigeminal ganglion revealed that the resp onses to repeated corneal applications of 30 mM zingerone show desensitizat ion. Cultured TG neurons, and oocytes expressing VR1 receptors, were also d esensitized by repeated applications of zingerone. Electrophysiological rec ordings revealed that these two vanilloids could activate the same receptor (VR1), currents in the same neuron, and cross-desensitize. The more rapid onset and shorter duration responses seen with zingerone (compared with cap saicin) provides a rationalization for its more rapid onset and shorter dur ation gustatory response. We attribute the different behavioral responses t o periodic applications of these two agonists to two competing effects: one leading to sensitization, and the other to tachyphylaxis. Which of these d ominates depends on the concentration, exposure time, and interstimulus int erval. Consequently, whether or not zingerone will exhibit tachyphylaxis de pends critically on the experimental conditions. (C) 2000 Elsevier Science Inc. All rights reserved.