Figure 4.
The cVc1.1 analogue, [C2H,C8F]cVc1.1, inhibits the mechanosensitivity of colonic nociceptors from healthy and CVH mice. (A) The mechanosensitivity of colonic nociceptors from healthy mice is reduced following increasing concentrations of [C2H,C8F]cVc1.1 applied to the mucosal epithelium, for 5 min at each concentration. Significant reductions in healthy colonic nociceptor mechanosensitivity relative to baseline responses were observed at 10, 100 nM and 1 μM. n = 8 afferents from N = 5 healthy mice. *P < 0.05; significantly different from baseline; one‐way ANOVA, with Bonferroni post hoc test. (B) [C2H,C8F]cVc1.1 potently and concentration‐dependently inhibited CVH nociceptors at 10, 100 nM and 1 μM. n = 9 afferents from N = 5 CVH mice. *P < 0.05; one‐way ANOVA, with Bonferroni post hoc test. (C) [C2H,C8F]cVc1.1 caused significantly more inhibition of CVH colonic nociceptors at 100 nM and 1 μM, compared with responses in healthy nociceptors. n = 8 afferents from N = 5 healthy mice, n = 9 afferents from N = 5 CVH mice. *P < 0.05; significantly different from helathy mice; two‐way ANOVA, with Bonferroni post hoc test. (D) Original recordings of a healthy colonic nociceptor, showing action potential firing in response to a 2 g vfh probe at baseline and in the presence of [C2H,C8F]cVc1.1 (1 μM). (E) Original recordings of a CVH colonic nociceptor showing action potential firing in response to a 2 g vfh probe at baseline (control) and in the presence of [C2H,C8F]cVc1.1 (1 μM).