Figure 2

Prolonged attenuation of responses to noxious thermal stimuli following intraplantar co-administration of MRS1477 and capsaicin. An infrared diode laser was used to preferentially stimulate Aδ- (A,C,E) or C-fibers (B,D,F,G) in the hind paw following intraplantar drug administration. At 2 h post-injection (A,B), rats treated with 2 μg MRS1477 + 30 μg CAP showed decreased nociceptive responses to both Aδ- and C-fiber stimuli, while rats treated with 1 μg MRS1477 + 30 μg CAP showed a significant attenuation of only C-fiber responses when compared to untreated controls. At 24 h post-injection (C,D), rats treated with 2 μg MRS1477 + 30 μg CAP still showed decreased responses to both Aδ- and C-fiber stimuli, and again 1 μg MRS1477 + 30 μg CAP-treated rats showed a significant increase in C-fiber withdrawal latency only. At 48 h post-treatment (E,F), rats receiving either 1 or 2 μg MRS1477 + 30 μg CAP displayed significantly reduced nociceptive responses under both stimulus paradigms when compared to 30 μg CAP-treated and untreated controls. Longitudinal C-fiber data are displayed for comparison (G). Since they were not significantly different from each other, data from the untreated and 30 μg CAP-only cohorts were combined in (G). * = p < 0.5; ** = p < 0.01; *** = p < 0.001; **** = p < 0.0001.