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Am J Physiol Regul Integr Comp Physiol 291: R307-R314, 2006. First published March 23, 2006; doi:10.1152/ajpregu.00824.2005
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Sex and Gender Differences in Pain and Inflammation

Sex differences in morphine-induced analgesia of visceral pain are supraspinally and peripherally mediated

Yaping Ji,1,2 Anne Z. Murphy,2,3 and Richard J. Traub1,2

1Department of Biomedical Sciences, 2Research Center for Neuroendocrine Influences on Pain, University of Maryland, Baltimore, Maryland; 3Georgia State University, Atlanta, Georgia

Submitted 23 November 2005 ; accepted in final form 14 March 2006

Increasing evidence suggests there is a sex difference in opioid analgesia of pain arising from somatic tissue. However, the existence of a sex difference in visceral pain and opioid analgesia is unclear. This was examined in the colorectal distention (CRD) model of visceral pain in the current study. The visceromotor response (vmr) to noxious CRD was recorded in gonadally intact male and female rats. Subcutaneous injection of morphine dose-dependently decreased the vmr in both groups without affecting colonic compliance. However, morphine was significantly more potent in male rats than females. Because systemic morphine can act at peripheral tissue and in the central nervous system (CNS), the source of the sex difference in morphine analgesia was determined. The peripherally restricted µ-opioid receptor (MOR) antagonist naloxone methiodide dose-dependently attenuated the effects of systemic morphine. Systemic administration of the peripherally restricted MOR agonist loperamide confirmed peripherally mediated morphine analgesia and revealed greater potency in males compared with females. Spinal administration of morphine dose-dependently attenuated the vmr, but there was no sex difference. Intracerebroventricular administration of morphine also dose-dependently attenuated the vmr with significantly greater potency in male rats. The present study documents a sex difference in morphine analgesia of visceral pain that is both peripherally and supraspinally mediated.

colorectal distention; male; female; µ opioid receptor; visceromotor response; intrathecal; intracerebroventricular


Address for reprint requests and other correspondence: R. Traub, Dept. of Biomedical Science, Univ. of Maryland Dental School, Rm. 5-A-22, 666 W. Baltimore St., Baltimore, MD 21201 (E-mail: rtraub{at}umaryland.edu)




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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
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.
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