FIGURE 1.

4‐aminoantipyrine (4‐AA) reduces the excitatory effect of capsaicin through CB₁ receptor activation in naive (non‐inflamed) conditions. (a) Local administration of capsaicin (CAP; 0.12 μg per paw) induces flinches. The capsaicin‐induced nociceptive behaviour is reduced by the administration of 4‐AA (160 μg per paw). AM251 (50 μg per paw) reversed the anti‐nociceptive effect of 4‐AA. *P< .05, significantly different from 0.9% NaCl, vehicle and (capsaicin+4‐AA). # P< .05, significantly different from 0.9% NaCl, vehicle, capsaicin and (capsaicin+4‐AA+AM251); one‐way ANOVA, with Tukey's test. (b–d) Representative recordings of calcium imaging from cultured primary sensory neurons. Capsaicin (500 nM) induces a rise in the intracellular calcium concentration ([Ca²⁺]_i; (b)) that is reversed by 4‐AA (100 μM; (c)). AM251 (10 μM) reversed the inhibitory effect of 4‐AA on the capsaicin‐induced calcium‐influx (ANOVA, Tukey's test, P < .05; (d)). (e) Average normalised amplitudes of capsaicin‐evoked changes in the [Ca²⁺]_i in various conditions. (f) Proportions of neurons responding the capsaicin at various conditions; 4‐AA reduces the proportion of neurons that respond to capsaicin and AM251 reduces the inhibitory effect of 4‐AA (Fisher's exact test, P < .05). In (e–f), *P< .05, significantly different from capsaicin and (capsaicin+4‐AA+AM251); one‐way ANOVA, with Tukey's test