Figure 1.
TRPV1 antagonist-induced hyperthermia is abolished in rats with localized abdominal desensitization of TRPV1 channels with a low dose of i.p. RTX. Rats pretreated with vehicle (sham-desensitized) responded to the i.v. administration of AMG0347 (a), AMG 517 (b), or AMG8163 (c) with a pronounced Tb rise, whereas no hyperthermic response occurred in rats desensitized with i.p. RTX (20 μg/kg). Doses of the TRPV1 antagonists used are indicated. In each panel, data plotted to the right of the temperature curves show two responses of the same sham-desensitized and desensitized rats that were used to study the hyperthermic effect of the corresponding TRPV1 antagonist: 1) the number of writhes (during 10 min) induced by the i.p. administration of RTX (0.1 μg/kg) and 2) the number of eye-wiping movements (during 5 min) induced by the epicorneal application of RTX solution (2 μg/ml, 20 μl). In all panels (a-c), vehicle-pretreated rats had a strong writhing reflex, whereas this reflex was absent in rats pretreated with i.p. RTX, thus confirming successful desensitization of TRPV1 channels in the peritoneal cavity by the latter pretreatment. In contrast, there was no difference between RTX-desensitized and sham-desensitized animals in the eye-wiping test, indicating that extra-abdominal TRPV1 channels were not affected by the i.p. RTX pretreatment. Here and in Figures 2–4, numbers in parentheses are the numbers of animals in the corresponding groups, and the data are presented as the mean ± SE.