Fig. 2.

(A) Male C57BL/6×129Sv mice were implanted with one placebo or morphine pellet. All mice showed Straub tail and characteristic stereotypic circling behavior within 30 min of morphine pellet administration. Morphine-treated mice showed decreased paw-withdrawal latencies compared to the placebo-treated animals 6 days following pellet implant, P<0.05, indicating morphine-induced hypersensitivity in these animals. Intrathecal administration of the NK-1 receptor antagonist 6 days post-morphine pellet reversed morphine-induced thermal hypersensitivity within 15 min post-administration, P<0.05, and this reversal lasted approximately 30 min, with paw-flick latencies back to pre-administration baselines 45 min post-administration of L-732,138. Intrathecal administration of L-732,138 did not alter paw-flick latencies of placebo-treated animals. (B) Male NK-1^−/− or NK-1^+/+ mice were implanted with one placebo or morphine pellet. NK-1^−/− mice had longer paw-withdrawal latencies compared to NK-1^+/+ mice throughout the testing period, P≤0.05. NK-1^+/+ mice treated with morphine showed decreased paw-withdrawal latencies compared to the NK-1^+/+ placebo-treated animals starting 3 days post-pellet implant, P≤0.05, indicating morphine-induced hypersensitivity in these animals. Morphine-pelleted NK-1^−/− mice showed paw-withdrawal latencies that were equivalent to placebo-pelleted NK-1^−/− mice across the entire 6-day testing period, indicating no morphine-induced hypersensitivity in these animals. * indicates significant difference from pre-pellet baselines.