FIGURE 5.

4‐AA desensitises TRPV1 channels, involving CB₁ receptors. (a) Average normalised amplitudes of primary sensory neurons to 4‐AA (1–50 μM) or capsaicin (CAPS; 500 nM) with and without PGE₂ (1 μM) pretreatment. Note that 4‐AA applied before capsaicin, at and above 10 μM, significantly reduces the amplitude of capsaicin‐evoked responses. *P< .05, significantly different from capsaicin alone; one‐way ANOVA with Tukey's test. (b) Representative recording of changes in the [Ca²⁺]_i from a cultured primary sensory neuron by the application of 4‐AA (10 μM), capsaicin (CAP; 500 nM) in the presence of PGE₂ (1 μM). Note that capsaicin induces only a small response. (c) Average normalised amplitudes of primary sensory neurons to 4‐AA (10 μM) and capsaicin (500 nM) in the presence of PGE₂ (1 μM) and without or with AM251 (10 μM) pretreatment. Note the opposing changes in the 4‐AA‐ and 4‐AA + capsaicin‐evoked increase in the [Ca2+]_i by AM251; while the 4‐AA‐induced responses are decreased, the 4‐AA + capsaicin‐evoked responses are increased. *P< .05, significantly different from capsaicin, #P< .05, significantly different from capsaicin, †P< .05, significantly different from 4‐AA, §P< .05, significantly different from (capsaicin+4‐AA); one‐way ANOVA with Tukey's test. (d) A typical recording of changes in the [Ca²⁺]_i by 4‐AA (10 μM) and capsaicin (500 nM) in the presence of PGE₂ (1 μM) and AM251 (10 μM) from a cultured primary sensory neuron. (e) AM251 (10 μM) attenuates the effect of 4‐AA on the number of capsaicin‐responding cells whereas it has no effect on the number of cells responsive to 4‐AA (Fisher's exact test, P < .05). *P< .05, significantly different from capsaicin, #P< .05, significantly different from capsaicin; one‐way ANOVA with Tukey's test