Sustained systemic delivery of the COMT inhibitor OR486 or 3 days of swim stress each produce pronounced (A, B) mechanical allodynia, (C, D) mechanical hyperalgesia, and (E, F) thermal heat hyperalgesia in both males and females. OR486 and swim stress together lead to significantly greater mechanical allodynia and mechanical hyperalgesia in males and females and greater thermal hyperalgesia only in females. Data are shown as Mean ± SD, N=6–9 per group. ***P < 0.001 different from the Vehicle+Sham group; ##P < 0.01, ###P < 0.001 different from the OR486+Sham group.