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. 2022 Oct 30;28(4):693-705.
doi: 10.5056/jnm21198.

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

Satoshi Sugino  1 , Ken Inoue  1 , Reo Kobayashi  1 , Ryohei Hirose  1 , Toshifumi Doi  1 , Akihito Harusato  1 , Osamu Dohi  1 , Naohisa Yoshida  1 , Kazuhiko Uchiyama  1 , Takeshi Ishikawa  1 , Tomohisa Takagi  1 , Hiroaki Yasuda  1 , Hideyuki Konishi  1 , Yasuko Hirai  2 , Katsura Mizushima  2 , Yuji Naito  2 , Toshifumi Tsuji  3 , Takashi Okuda  3 , Keizo Kagawa  3 , Makoto Tominaga  4 , Yoshito Itoh  1
Affiliations

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

Satoshi Sugino et al. J Neurogastroenterol Motil. .

Abstract

Background/aims: Several 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.

Methods: In 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).

Results: In 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.

Conclusion: For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.

Keywords: Animals; Colon; Peristalsis; Single-blind method; Temperature.

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Conflict of interest statement

Conflicts of interest: None.

Figures

Figure 1
Figure 1
Patient allocation of clinical trial.
Figure 2
Figure 2
Reduction of colonic motor activity and intraluminal high-amplitude pressure by cold saline in rats. (A) The colonic motility and intraluminal high-amplitude pressure after administration of room temperature saline. (B) A typical pattern of reduction of colonic motility and intraluminal high-amplitude pressure induced by 5°C saline. (C) Serial photographs of colonic motor activity. Left: motility before treatment. Right: motility after treatment with 5°C saline.
Figure 3
Figure 3
In clinical trial, the ratio of patients who did not show any peristalsis (grade 0) after mildly cool water or room temperature water was administered as a direct spray to the colonic mucosa. *P < 0.05 in comparison to room temperature water (chi-squared test).
Figure 4
Figure 4
Suppression of peak frequency (PF) after the administration of 5°C saline in rats. (A) Decreased ratio of PF in high-amplitude pressure following the administration of 5°C saline. To quantify the decrease in high-amplitude pressure induced by 5°C saline, the ratio of contraction frequency before and after administration with a length of more than 8 mm was calculated as the %PF. *P < 0.05 vs room temperature. (B) The area under the curve (AUC) at high-amplitude pressure with 5°C saline. The AUC was calculated before and after drug administration using the lowest intraluminal pressure value as the baseline. There were no significant differences among the 3 groups. (C) The results of the peak pressure amplitude (PPA) at high-amplitude pressure with 5°C saline. The difference between PPA and the lowest intraluminal pressure was defined as PPA, and the ratio of PPA before and after medication was calculated as % PPA. There was no significant difference among the 3 groups (n = 5).
Figure 5
Figure 5
Colonic motility in wild type (WT) mice and transient receptor potential melastatin 8 (TRPM8)-deficient (TRPM8–/–) mice. The intraluminal high-amplitude pressure and colonic motor activity before and after administration of 5°C saline in wild type (WT) mice. A typical pattern of reduction of colonic motor activity and intraluminal high-amplitude pressure induced by 5°C saline. (D) The colonic motility and intraluminal high-amplitude pressure before and after administration of 5°C saline in transient receptor potential melastatin 8-deficient (TRPM8)–/– mice. (E) Decreased ratio of peak frequency (PF) in high-amplitude pressure following administration of 5°C saline in WT mice. To quantify the decrease in high-amplitude pressure induced by 5°C saline, the ratio of contraction frequency before and after administration with a length of more than 8 mm was calculated as the %PF. *P < 0.05 vs room temperature (25°C) of wild type mice. (F) The area under the curve (AUC) at high-amplitude pressure with 5°C saline. The AUC was calculated before and after saline administration using the lowest intraluminal pressure value as the baseline. There were no significant differences between the 2 groups. (G) The results of the peak pressure amplitude (PPA) at high-amplitude pressure with 5°C saline. The difference between PPA and the lowest intraluminal pressure was defined as PPA, and the ratio of PPA before and after medication was calculated as %PPA. There were no significant differences between the 2 groups (n = 6).
Figure 6
Figure 6
Colonic motility in rats without or with the administration of a transient receptor potential ankyrin 1 (TRPA1) inhibitor. (A) Decreased ratio of peak frequency (PF) in high-amplitude pressure following the administration of 5°C saline in rats without administration of a TRPA1 inhibitor. To quantify the decrease in high-amplitude pressure induced by 5°C saline, the ratio of contraction frequency before and after administration with a length of more than 8 mm was calculated as the %PF. **P < 0.01 vs room temperature (25°C) without a TRPA1 inhibitor, ***P < 0.001 vs room temperature (25°C) with a TRPA1 inhibitor. (B) The area under the curve (AUC) at high-amplitude pressure with 5°C saline. The AUC was calculated before and after administration of saline using the lowest intraluminal pressure value as the baseline. There were no significant differences between the 2 groups. (C) Results of the peak pressure amplitude (PPA) at high-amplitude pressure with 5°C saline. The difference between the PPA and the lowest intraluminal pressure was defined as the PPA, and the ratio of the PPAs before and after medication was calculated as the %PPA. There were no significant differences between the 2 groups (n = 3).
Figure 7
Figure 7
Transient receptor potential melastatin 8 (TRPM8) localization in the TRPM8 green fluorescent protein (GFP) mouse colon. (A) GFP-targeted polyclonal antibody staining in the TRPM8 GFP mouse colon. (B) GFP staining in C57BL/6J mice. No detectable signal was observed. (C) Enlarged (×2 zoom) view of GFP staining in c57bl6 mice. No detectable signal was observed. (D) Enlarged (×2 zoom) view of a section of the TRPM8 GFP mouse colon. (E) Enlarged (×2 zoom) view of a section of the TRPM8 GFP mouse colon. (E) Calcitonin gene-related peptide (CGRP) staining in the TRPM8 GFP mouse colon. (G) Merged image showing TRPM8 and CGRP expressing cells in the TRPM8 GFP mouse colon.
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References

    1. Inoue K, Dohi O, Gen Y, et al. L-menthol improves adenoma detection rate during colonoscopy: a randomized trial. Endoscopy. 2014;46:196–202. doi: 10.1055/s-0034-1365035. - DOI - PubMed
    1. Mearin F, Lacy BE, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150:1393–1407. e5. doi: 10.1053/j.gastro.2016.02.031. - DOI - PubMed
    1. Drossman DA. Functional gastrointestinal disorders: history, pathophysiology, clinical features and rome IV. Gastroenterology. 2016;150:1262–1279. e2. doi: 10.1053/j.gastro.2016.02.032. - DOI - PubMed
    1. Sun WM, Houghton LA, Read NW, Grundy DG, Johnson AG. Effect of meal temperature on gastric emptying of liquids in man. Gut. 1988;29:302–305. doi: 10.1136/gut.29.3.302. - DOI - PMC - PubMed
    1. Church JM. Warm water irrigation for dealing with spasm during colonoscopy: simple, inexpensive, and effective. Gastrointest Endosc. 2002;56:672–674. doi: 10.1016/S0016-5107(02)70115-6. - DOI - PubMed

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