A putative anti‐inflammatory role for TRPM8 in irritable bowel syndrome—An exploratory study. Issue 9 (19th June 2021)

• Record Type: Journal Article
• Authors: Peiris, Madusha; Weerts, Zsa Zsa R. M.; Aktar, Rubina; Masclee, Ad A. M.; Blackshaw, Ashley; Keszthelyi, Daniel
• Is Part Of: Neurogastroenterology & motility. Volume 33:Issue 9(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-06-19
• Subjects: Gastrointestinal system -- Motility -- Periodicals; Gastrointestinal system -- Innervation -- Periodicals; 616.33
• DOI: 10.1111/nmo.14170
• Languages: English
• ISSNs: 1350-1925

Abstract

Abstract: Background: Chronic and recurring pain is a characteristic symptom in irritable bowel syndrome (IBS). Altered signaling between immune cells and sensory neurons within the gut may promote generation of pain symptoms. As transient receptor potential melastatin 8 (TRPM8) agonists, such as L‐menthol in peppermint oil, have shown to attenuate IBS pain symptoms, we began investigating potential molecular mechanisms. Methods: Colonic biopsy tissues were collected from patients with IBS and controls, in two separate cohorts. Immunohistochemistry was performed to identify TRPM8 localization. Quantitative PCR was performed to measure mucosal mRNA levels of TRPM8. In addition, functional experiments with the TRPM8 agonist icilin were performed ex vivo to examine cytokine release from biopsies. Daily diaries were collected to ascertain pain symptoms. Results: In biopsy tissue from IBS patients, we showed that TRPM8 immunoreactivity is colocalized with immune cells predominantly of the dendritic cell lineage, in close approximation to nerve endings, and TRPM8 protein and mRNA expression was increased in IBS patients compared to controls ( p < 0.001). TRPM8 mRNA expression showed a significant positive association with abdominal pain scores ( p = 0.015). Treatment of IBS patient biopsies with icilin reduced release of inflammatory cytokines IL‐1β, IL‐6, and TNF‐α ( p < 0.05). Conclusions and inferences: These data indicate TRPM8 may have important anti‐inflammatory properties and by this virtue can impact neuro‐immune disease mechanisms in IBS. Abstract : TRPM8 expressed on dendritic cell types can be modulated by icilin to reduce inflammatory cytokine release in irritable bowel syndrome (IBS) patients. These data suggest neuro‐immune pathways are important in IBS disease modulation.