TRP (transient receptor potential) channels were first described in Drosophila in 1989, and in mammals, TRP channels comprise six related protein families (TRPC, TRPV, TRPM, TRPA, TRPML, TRPP). One subunit of the TRP channel is composed of six transmembrane domains and a putative pore region with both amino and carboxyl termini on the cytosolic side. It is thought that the subunits form functional channels as homo- or hetero-tetramers. TRP channels are best recognized for their contributions to sensory transduction, responding to temperature, nociceptive stimuli, touch, osmolarity, pheromones and other stimuli from both within and outside the cell. Among the huge TRP super family of ion channels, some have been proven to be involved in thermosensation detecting ambient temperatures from cold to hot. There are now ten thermosensitive TRP channels (TRPV1, TRPV2, TRPV3, TRPV4, TRPM2, TRPM3, TRPM4, TRPM5, TRPM8 and TRPA1) with distinct temperature thresholds for their activation. Because temperature ranges above 43 degree C or below 15 degree C are considered to cause pain sensation in our body, thermosensitive TRP channels whose temperature thresholds are in the range can be viewed as nocicpetive receptors as well. Thermosensitive TRP channels work as ‘multimodal receptors’ which respond to various chemical and physical stimuli. TRPV1, the first identified thermosensitive TRP channel, was found as a receptor for capsaicin, and later was found to have thermosensitivity. I would like to talk about the physiological significance of the thermosensitive TRP channels (TRPV1, TRPA1, TRPV4 and TRPM2). Some of the thermosensitive TRP channels are expressed in the tissues not exposed to the dynamic changes in the ambient temperature and activated by warm temperature around our body temperature, suggesting that they have some specific physiological functuions. In addition, how structure and functions of thermosensitive TRP channels were changed dynamically in the process of evolution will also be discussed.

Background/Aims: Endoscopic resection of all colorectal adenomatous lesions with a low complication rate, simplicity, and negative residuals is challenging. Hence, we developed a new method called “non-injection resection using bipolar soft coagulation mode (NIRBS)” method, adapted for colorectal lesions. In addition, we evaluated the effectiveness of this method. Methods: We performed NIRBS throughout a 12-month period for all colorectal lesions which snare resection was acceptable without cancerous lesions infiltrating deeper than the submucosal layer. Results: A total of 746 resected lesions were included in the study, with a 4.5 mm mean size (range, 1–35 mm). The major pathological breakdowns were as follows: 64.3% (480/746) were adenomas, and 5.0% (37/746) were intraepithelial adenocarcinomas (Tis lesions). No residuals were observed in any of the 37 Tis lesions (mean size, 15.3 mm). Adverse events included bleeding (0.4%) but no perforation. Conclusions NIRBS allowed the resection of multiple lesions with simplicity because of the non-injection and without perforating due to the minimal burn effect of the bipolar snare set in the soft coagulation mode. Therefore, NIRBS can be used to resect adenomatous lesions easily, including Tis lesions, from small to large lesions without leaving residuals.

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 temperaturetreated 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.