Figure 4

Rectal biopsy supernatants from PI-IBS patients sensitize TRPV1 on murine DRG neurons mediated by histamine via the Hrh1. Effect of overnight incubation of murine DRG neurons with supernatant of cultured rectal biopsies of PI-IBS patients (n = 8) or HV (n = 8) on the Ca²⁺ response (A) and percentage of responding neurons (B) to capsaicin (10 nM). Data are shown as median + interquartile range. (*p < 0.001, Mann Whitney U test). (C,D) Data showing the capsaicin-induced Ca²⁺ response after overnight incubation with supernatant of cultured rectal biopsies of PI-IBS patients (n = 8) in the presence or absence of pyrilamine (1 µM) (+P) (n = 8) and in histamine 1 receptor knock-out (Hrh1 KO) mice (n = 5) (C) Effect of overnight incubation with HV supernatants (n = 8) supplemented with histamine (10 µM) (+H) (n = 8) or histamine (10 µM) and pyrilamine (1 µM) (+H + P) (n = 4) or in Hrh1 KO mice (n = 5) on the Ca²⁺ response to capsaicin (D). Data are shown as mean + standard error of the mean (SEM). *p < 0.001 Statistical analysis by One-way ANOVA (E) Histamine levels were normalized to the weight of biopsy and compared in rectal biopsy supernatants of HV (n = 9) versus PI-IBS (n = 8) patients. Mann-Whitney U test. H = histamine, HV = healthy volunteer, P = pyrilamine, PI-IBS = post-infectious irritable bowel syndrome, Hrh1 KO = histamine 1 receptor knock-out.