(A) Application of the TGR5 agonist deoxycholic acid (DCA; 100 μM) to the colonic mucosa of CVH mice induces mechanical hypersensitivity of colonic nociceptors (**P < 0.01, N = 7). Dots represent values from individual CVH afferents before and after DCA application. Lower panels show representative recordings from a single colonic afferent nerve fiber from a CVH mouse responding to a 2 g vfh before and after incubation with DCA. (B) Application of the TGR5 agonist oleanolic acid (OA; 100 μM for 5 minutes) also caused mechanical hypersensitivity in nociceptors from CVH mice (**P < 0.01, N = 8). (C) The TGR5 agonist CCDC (100 μM for 5 minutes) also evoked mechanical hypersensitivity of colonic nociceptors from CVH mice (*P < 0.05, N = 7). (D) Colonic nociceptors from CVH mice also displayed mechanical hypersensitivity to the application of the MrgprA3 agonist chloroquine (CQ, 10 μM for 5 minutes, *P < 0.05, N = 9), (E) MrgprC11 agonist BAM8-22 (20 μM for 5 minutes, **P < 0.01, N = 9), and (F) the combined MrgprC11/MrgprA4 agonist neuropeptide FF (NPFF; 5 μM for 5 minutes, **P < 0.01, N = 9 mice). Data represent Mean ± SEM. P values determined by paired t tests (A–F).