Association Between the Cool Temperature-dependent Suppression of Colonic Peristalsis and Transient Receptor Potential Melastatin 8 Activation in Both a Randomized Clinical Trial and an Animal Model

• Published in: Journal of neurogastroenterology and motility 2022-10, Vol.28 (4), p.693-705
• Main Authors: Sugino, Satoshi, Inoue, Ken, Kobayashi, Reo, Hirose, Ryohei, Doi, Toshifumi, Harusato, Akihito, Dohi, Osamu, Yoshida, Naohisa, Uchiyama, Kazuhiko, Ishikawa, Takeshi, Takagi, Tomohisa, Yasuda, Hiroaki, Konishi, Hideyuki, Hirai, Yasuko, Mizushima, Katsura, Naito, Yuji, Tsuji, Toshifumi, Okuda, Takashi, Kagawa, Keizo, Tominaga, Makoto, Itoh, Yoshito
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 2093-0879; 2093-0887
• DOI: 10.5056/jnm21198

Background/AimsSeveral studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. MethodsIn the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). ResultsIn the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperature-treated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. ConclusionFor the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.