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A novel role for TRPM8 in visceral afferent function.
Pain. 2011 Jul; 152(7):1459-1468.PAIN

Abstract

Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperatures and cooling agents, such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of bowel hypersensitivity; however, the underlying mechanisms of action are unclear. Here we determined the role of TRPM8 in colonic sensory pathways. Laser capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, and retrograde tracing were used to localise TRPM8 to colonic primary afferent neurons. In vitro extracellular single-fibre afferent recordings were used to determine the effect of TRPM8 channel activation on the chemosensory and mechanosensory function of colonic high-threshold afferent fibres. TRPM8 mRNA was present in colonic DRG neurons, whereas TRPM8 protein was present on nerve fibres throughout the wall of the colon. A subpopulation (24%, n=58) of splanchnic serosal and mesenteric afferents tested responded directly to icilin (5 μmol/L). Subsequently, icilin significantly desensitised afferents to mechanical stimulation (P<.0001; n=37). Of the splanchnic afferents responding to icilin, 21 (33%) also responded directly to the TRPV1 agonist capsaicin (3 μmol/L), and icilin reduced the direct chemosensory response to capsaicin. Icilin also prevented mechanosensory desensitization and sensitization induced by capsaicin and the TRPA1 agonist AITC (40 μmol/L), respectively. TRPM8 is present on a select population of colonic high threshold sensory neurons, which may also co-express TRPV1. TRPM8 couples to TRPV1 and TRPA1 to inhibit their downstream chemosensory and mechanosensory actions.

Authors+Show Affiliations

Nerve-Gut Research Laboratory, Department of Gastroenterology & Hepatology, Hanson Institute, Royal Adelaide Hospital, Adelaide, South Australia, Australia Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia Discipline of Physiology, University of Adelaide, Adelaide, South Australia, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21489690

Citation

Harrington, Andrea M., et al. "A Novel Role for TRPM8 in Visceral Afferent Function." Pain, vol. 152, no. 7, 2011, pp. 1459-1468.
Harrington AM, Hughes PA, Martin CM, et al. A novel role for TRPM8 in visceral afferent function. Pain. 2011;152(7):1459-1468.
Harrington, A. M., Hughes, P. A., Martin, C. M., Yang, J., Castro, J., Isaacs, N. J., Blackshaw, A. L., & Brierley, S. M. (2011). A novel role for TRPM8 in visceral afferent function. Pain, 152(7), 1459-1468. https://doi.org/10.1016/j.pain.2011.01.027
Harrington AM, et al. A Novel Role for TRPM8 in Visceral Afferent Function. Pain. 2011;152(7):1459-1468. PubMed PMID: 21489690.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel role for TRPM8 in visceral afferent function. AU - Harrington,Andrea M, AU - Hughes,Patrick A, AU - Martin,Christopher M, AU - Yang,Jing, AU - Castro,Joel, AU - Isaacs,Nicole J, AU - Blackshaw,Ashley L, AU - Brierley,Stuart M, Y1 - 2011/04/13/ PY - 2010/07/15/received PY - 2010/11/24/revised PY - 2011/01/14/accepted PY - 2011/4/15/entrez PY - 2011/4/15/pubmed PY - 2011/10/14/medline SP - 1459 EP - 1468 JF - Pain JO - Pain VL - 152 IS - 7 N2 - Transient receptor potential ion channel melastatin subtype 8 (TRPM8) is activated by cold temperatures and cooling agents, such as menthol and icilin. Compounds containing peppermint are reported to reduce symptoms of bowel hypersensitivity; however, the underlying mechanisms of action are unclear. Here we determined the role of TRPM8 in colonic sensory pathways. Laser capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, and retrograde tracing were used to localise TRPM8 to colonic primary afferent neurons. In vitro extracellular single-fibre afferent recordings were used to determine the effect of TRPM8 channel activation on the chemosensory and mechanosensory function of colonic high-threshold afferent fibres. TRPM8 mRNA was present in colonic DRG neurons, whereas TRPM8 protein was present on nerve fibres throughout the wall of the colon. A subpopulation (24%, n=58) of splanchnic serosal and mesenteric afferents tested responded directly to icilin (5 μmol/L). Subsequently, icilin significantly desensitised afferents to mechanical stimulation (P<.0001; n=37). Of the splanchnic afferents responding to icilin, 21 (33%) also responded directly to the TRPV1 agonist capsaicin (3 μmol/L), and icilin reduced the direct chemosensory response to capsaicin. Icilin also prevented mechanosensory desensitization and sensitization induced by capsaicin and the TRPA1 agonist AITC (40 μmol/L), respectively. TRPM8 is present on a select population of colonic high threshold sensory neurons, which may also co-express TRPV1. TRPM8 couples to TRPV1 and TRPA1 to inhibit their downstream chemosensory and mechanosensory actions. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/21489690/A_novel_role_for_TRPM8_in_visceral_afferent_function_ L2 - https://linkinghub.elsevier.com/retrieve/pii/00006396-201107000-00008 DB - PRIME DP - Unbound Medicine ER -