TRPV1 is required for the inhibitory effect of capsaicin on the neuronal excitability and formalin-induced nociceptive response. (A) Treatment with TRPV1 antagonist, capsazepine, attenuated the capsaicin-induced reduction in action potential frequency in small DRG neurons (n = 13). (B, C, D) Whole-cell patch-clamp recording showed that the capsaicin-induced reduction of action potential frequency in capsaicin-sensitive small DRG neurons (for 2 μM capsaicin, 10 positive neurons out of 34; for 1 mM capsaicin, 8 positive neurons out of 22) dissociated from TRPV1+/+ littermates was absent in small DRG neurons from TRPV1−/− mice (for 2 μM capsaicin, n = 31; for 1 mM capsaicin, n = 10). (E) The licking time in both phase I and phase II of mice induced by 2% formalin was not affected by intraplantar pre-injection of 10 μg capsaicin (n = 8), compared to vehicle group (n = 8). Data are shown as mean ± SEM.