| Summary: | Objective To investigate the role of transient receptor potential ankyrin 1 (TRPA1) in the recovery of colonic motility following pelvic nerve denervation (PND) in mice. Methods A total of 108 male C57 mice were randomized into PND model group (n=54) and sham operation group (n=54), and in each group, the mice were further randomized into untreated group, TRPA1 agonist (curcumin) treatment group, and TRPA1 antagonist (HC-030031) treatment group. Another 30 male TRPA1 knockout mice were also randomized into PND group (n=15) and sham operation group (n=15). All the mice underwent open surgery for PND by severing the pelvic nerve or received sham operation, and during the operation, a silicone tube was embedded in the cecum near the colon for testing colonic transit function on postoperative days 1, 3, and 7. Results Compared with the sham-operated mice, the PND mice showed significantly decreased colonic transit function on postoperative days 1 (P < 0.001) and 3 (P=0.040) but had comparable transit function on day 7. Compared with the sham-operated mice without any interventions (control group), curcumin treatment resulted in significantly enhanced colonic transit function in the sham-operated mice (P < 0.001), and promoted nearly full recovery of colonic transit function in PND mice on postoperative days 1 (P=0.304 vs control) and 3 (P=0.304 vs control) and even further enhancement on day 7 (P=0.001). In PND mice, treatment with the TRPA1 antagonist HC-030031 significantly lowered colonic transit function (P < 0.05) without any signs of recovery. The results of colonic transit test in TRPA1 knockout mice were consistent with those in HC-030031-treated PND mice. The results of immunohistochemistry showed that TRPA1 was expressed in the colonic mucosa of the mice, and PND caused a transient decrease in TRPA1 expression followed by a gradual recovery. Conclusion The colonic motility shows an adaptive recovery mechanism after PND in mice. TRPA1, which is expressed in the colonic mucosa of mice, can significantly promote colonic motility recovery following PND in mice.
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