Fig. 6.
Antagonism of TRPV1 attenuated mechanosensitivity of stretch-sensitive colorectal afferents. A: relative to vehicle (1% 1-methyl-2-pyrrolidinone, 1M2P), A889425 did not significantly decrease stretch-response functions of muscular afferents at any concentration tested although 300 nM reduced responses to ∼60%. Application of an effect criterion of ≥15% posttreatment reduction of stretch-responsive functions (9/14 fibers; ∼65% of total) revealed significant attenuation by 300 nM A889425 of response to stretch (F3,120 = 10.5, *P < 0.001). B: 3 μM A889425 significantly attenuated muscular/mucosal stretch-response functions relative to vehicle (F3,102 = 2.9, *P < 0.05). Application of the effect criterion as above (8/12 fibers; ∼65%) similarly yielded significant attenuation by 3 μM A889425 of response to stretch (F3,90 = 4.8, P < 0.01). C and D: response thresholds of muscular and muscular/mucosal afferents, with or without application of the effect criterion, were unaffected by A889425. For statistical analyses, responses post-A889425 were compared against responses post-1M2P, which were compared against their respective predrug baselines. n = number of fibers/group. >15% denotes application of response criterion.