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.
journal_name
Painjournal_title
Painauthors
Harrington AM,Hughes PA,Martin CM,Yang J,Castro J,Isaacs NJ,Blackshaw AL,Brierley SMdoi
10.1016/j.pain.2011.01.027subject
Has Abstractpub_date
2011-07-01 00:00:00pages
1459-1468issue
7eissn
0304-3959issn
1872-6623pii
00006396-201107000-00008journal_volume
152pub_type
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