Analgesic effects of amiloride (ami.; 200 μM) and capsazepine (CPZ; 100 μM) on acid-evoked pain in human subjects at various pH stages. Mean ± SE are shown for each data point. (a) Effects of amiloride on pH 6.5– and 7.0–induced pain (n = 10). The intensity of provoked painful sensation was attenuated in a pH-dependent manner with lowering proton concentration. Amiloride treatment potently suppressed the acid-evoked pain down to the pH 7.4 control level (*P < 0.01 vs. second pH 6.5 treatments; **P < 0.01 vs. pH 7.0 treatments). (b) Effects of the amiloride and capsazepine on pH 5.0–induced pain (n = 10). The analgesic effects of the amiloride at pH 5.0 were less potent than those observed at pH greater than or equal to 6.0, while the capsazepine displayed partial blocking effects on the pain instead (*P < 0.01 and **P < 0.05 vs. second pH 5.0 treatments). Simultaneous applications of both drugs almost completely abolished the pain (***P < 0.05).