Figure 3.
Effect of C11-DOPri2 on DOP receptor-mediated antihyperalgesia and antinociception. (A) Sprague-Dawley rats were injected with CFA in the plantar surface of the hindpaw. Thirty minutes before the CFA injection and every 12 h thereafter, rats were injected i.t. with C11-DOPri2 (6 and 15 μg) or C11-DOPrscrambled peptides (6 and 15 μg). Seventy-two hours after the CFA injection, paw withdrawal latencies (in s) to noxious heat (plantar test) were recorded every 15 min (from 0 to 60 min) following Dlt II administration (10 μg, i.t.). I.t.-administered C11-DOPri2 (6 and 15 μg) induced a significant decrease in DOP receptor-mediated antihyperalgesia. ****P < 0.0001. (B) Sprague-Dawley rats injected s.c. once every 12 h with escalating doses of morphine (5, 8, 10 and 15 mg·kg−1) received i.t. injections of C11-DOPri2 (6 and 15 μg) or C11-DOPrscrambled (6 and 15 μg) 30 min before each morphine injection. Twelve hours after the last morphine injection, tail flick latencies (in s) were measured every 10 min (from 0 to 60 min) after Dlt II injection (10 μg, i.t.) using the tail immersion test. C11-DOPri2 induced a significant decrease in DOP receptor-mediated antinociception. **P < 0.01. (C) Results presented in (A) are expressed as the AUC obtained between 0 and 60 min after Dlt II injection (the Y-axis baseline was set for each animal according to their latency to paw withdrawal after inflammation). *P < 0.05. (D) Results presented in (B) are expressed as the AUC obtained between 0 and 60 min after Dlt II injection (the Y-axis baseline was set for each animal according to their latency to tail withdrawal at 0 min). **P < 0.01. Numbers given in parentheses represent the number of animals per group.