Progesterone rapidly recruits female-typical opioid-induced hyperalgesic mechanisms

Continuous morphine treatment can paradoxically increase nociception (i e hyperalgesia) in male and female mice but sex differences have been reported Here we studied progesterone modulation of these differences by assessing nociception on the tail-withdrawal test in male and female mice rendered hyperalgesic during continuous infusion of two different morphine doses (1 6 and 400 mg/kg/24 h) Although the lower morphine infusion dose increased nociception in both sexes by infusion Day 4 this hyperalgesia dissipated by Day 6 in males and ovariectomized females but not gonadally intact females A single subcutaneous progesterone (0 0016 mg/kg) injection to males and ovariectomized females on Day 6 caused hyperalgesia to recur within 30 min and to persist for a minimum of 120 min The larger morphine infusion dose also increased nociception in both sexes on Days 4 and 6 However the NMDA receptor antagonist MK-801 (0 05 mg/kg) reversed hyperalgesia in males and ovariectomized females but not gonadally intact females on infusion Day 6 Subcutaneous progesterone (0 0016 mg/kg) injection inhibited this reversal in male and ovariectomized female mice but had no effect on nociception in saline-infused mice of either sex These data confirm our previous findings that male and female mice utilize distinct hyperalgesic mechanisms and show for the first time that a single progesterone bolus dose can recruit female-typical hyperalgesia in ovariectomized females and males (C) 2010 Elsevier Inc All rights reserved