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Sex and Gender Differences in Pain and Inflammation

Persistent pain model reveals sex difference in morphine potency

¹Department of Biology, Center for Behavioral Neuroscience, Georgia State University, Atlanta, Georgia; and ²Department of Biological Sciences, Dental School, ³Research Center for Neuroendocrine Influences on Pain, University of Maryland, Baltimore, Maryland

Submitted 10 January 2006 ; accepted in final form 14 February 2006

Central or systemic administration of agonists directed at the µ or opiate receptors generally produce a greater degree of analgesia in males than in females. To date, most studies examining sex-based differences in opioid analgesia have used acute noxious stimuli (i.e., tail-flick and hot plate test); thus the potential dimorphic response of centrally acting opiates in the alleviation of persistent inflammatory pain is not well established. In the present study, right hind paw withdrawal latency (PWL) to radiant thermal stimuli was measured in intact male and cycling female Sprague-Dawley rats before and after unilateral hind paw injection of the inflammatory agent complete Freund's adjuvant (CFA). Control animals received intraplantar injection of saline. Twenty four hours after CFA or saline injection, animals received either saline or morphine bisulfate (0.5–15 mg/kg sc). Separate groups of control or inflamed animals were tested on their responsiveness to morphine at 7, 14, and 21 days post-CFA or saline. No sex differences were noted for baseline PWLs, and females displayed slightly less thermal hyperalgesia at 24 h post-CFA. At all morphine doses administered, both the antihyperalgesic effects of morphine in the inflamed animals and the antinociceptive effects of morphine in control animals were significantly greater in males compared with females. Similarly, in males, the antihyperalgesic effects of morphine increased significantly at 7–21 days post-CFA; no significant shift in morphine potency was noted for females. These studies demonstrate sex-based differences in the effects of morphine on thermal hyperalgesia in a model of persistent inflammatory pain.

antinociception; antihyperalgesic; inflammation; opioids

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				Y. Ji, A. Z. Murphy, and R. J. Traub Sex differences in morphine-induced analgesia of visceral pain are supraspinally and peripherally mediated Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R307 - R314. [Abstract] [Full Text] [PDF]

				K. J. Berkley, S. S. Zalcman, and V. R. Simon Sex and gender differences in pain and inflammation: a rapidly maturing field Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R241 - R244. [Full Text] [PDF]