RESEARCH ARTICLE Differential Contribution of TRPA1, TRPV4 and TRPM8 to Colonic Nociception in Mice

Background Various transient receptor potential (TRP) channels in sensory neurons contribute to the transduction of mechanical stimuli in the colon. Recently, even the cold-sensing menthol re-ceptor TRPM(melastatin)8 was suggested to be involved in murine colonic mechano-nociception. Methods To analyze the roles of TRPM8, TRPA1 and TRPV4 in distension-induced colonic nocicep-tion and pain, TRP-deficient mice and selective pharmacological blockers in wild-type mice (WT) were used. Visceromotor responses (VMR) to colorectal distension (CRD) in vivo were recorded and distension/pressure-induced CGRP release from the isolated murine colon ex vivo was measured by EIA. Results Distension-induced colonic CGRP release was markedly reduced in TRPA1-/- and TRPV4-/-mice at 90/150 mmHg compared to WT. In TRPM8-deficient mice the reduction was onl