QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (83) Citing Articles via Google Scholar Google Scholar Articles by Zubieta, J.-K. Articles by Stohler, C. S. Search for Related Content PubMed PubMed Citation Articles by Zubieta, J.-K. Articles by Stohler, C. S.

 Previous Article  |  Next Article 

The Journal of Neuroscience, June 15, 2002, 22(12):5100-5107

µ-Opioid Receptor-Mediated Antinociceptive Responses Differ in Men and Women

Jon-Kar Zubieta^{1, 2}, Yolanda R. Smith³, Joshua A. Bueller¹, Yanjun Xu¹, Michael R. Kilbourn², Douglas M. Jewett², Charles R. Meyer², Robert A. Koeppe², and Christian S. Stohler⁴

¹ Department of Psychiatry and Mental Health Research Institute, Departments of ² Radiology and ³ Obstetrics and Gynecology, Medical School, and ⁴ Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109

Sex differences in the experience of clinical and experimental pain have been reported. However, the neurobiological sources underlying the variability in pain responses between sexes have not been adequately explored, especially in humans. The endogenous opioid neurotransmitters and µ-opioid receptors are centrally implicated in responses to stress, in the suppression of pain, and in the action of opiate analgesic drugs. Here we examined sex differences in the activation of the µ-opioid system in response to an intensity-controlled sustained deep-tissue pain challenge with positron emission tomography and a µ-opioid receptor-selective radiotracer. Twenty-eight young healthy volunteers (14 men and 14 women) were studied during saline control and pain conditions using a double-blind, randomized, and counterbalanced design. Women were scanned during the early follicular phase of their menstrual cycles after ovulatory cycles. Significant sex differences in the regional activation of the µ-opioid system in response to sustained pain were detected compared with saline controls. Men demonstrated larger magnitudes of µ-opioid system activation than women in the anterior thalamus, ventral basal ganglia, and amygdala. Conversely, women demonstrated reductions in the basal state of activation of the µ-opioid system during pain in the nucleus accumbens, an area previously associated with hyperalgesic responses to the blockade of opioid receptors in experimental animals. These data demonstrate that at matched levels of pain intensity, men and women during their follicular phase differ in the magnitude and direction of response of the µ-opioid system in distinct brain nuclei.

Key words: µ-opioid receptors; endogenous opioids; pain; sex differences; positron emission tomography; thalamus; nucleus accumbens; ventral pallidum; substantia innominata; amygdala

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22125100-08$05.00/0

This article has been cited by other articles:

				S. D. Mague, C. Isiegas, P. Huang, L.-Y. Liu-Chen, C. Lerman, and J. A. Blendy Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior PNAS, June 30, 2009; 106(26): 10847 - 10852. [Abstract] [Full Text] [PDF]

				B. J. Mickey, F. Ducci, C. A. Hodgkinson, S. A. Langenecker, D. Goldman, and J.-K. Zubieta Monoamine Oxidase A Genotype Predicts Human Serotonin 1A Receptor Availability In Vivo J. Neurosci., October 29, 2008; 28(44): 11354 - 11359. [Abstract] [Full Text] [PDF]

				F. Eippert, U. Bingel, E. Schoell, J. Yacubian, and C. Buchel Blockade of Endogenous Opioid Neurotransmission Enhances Acquisition of Conditioned Fear in Humans J. Neurosci., May 21, 2008; 28(21): 5465 - 5472. [Abstract] [Full Text] [PDF]

				G. Henriksen and F. Willoch Imaging of opioid receptors in the central nervous system Brain, May 1, 2008; 131(5): 1171 - 1196. [Abstract] [Full Text] [PDF]

				D. J. Scott, C. S. Stohler, C. M. Egnatuk, H. Wang, R. A. Koeppe, and J.-K. Zubieta Placebo and Nocebo Effects Are Defined by Opposite Opioid and Dopaminergic Responses Arch Gen Psychiatry, February 1, 2008; 65(2): 220 - 231. [Abstract] [Full Text] [PDF]

				S. E. Kennedy, R. A. Koeppe, E. A. Young, and J.-K. Zubieta Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women. Arch Gen Psychiatry, November 1, 2006; 63(11): 1199 - 1208. [Abstract] [Full Text] [PDF]

				D. J. Scott, M. M. Heitzeg, R. A. Koeppe, C. S. Stohler, and J.-K. Zubieta Variations in the human pain stress experience mediated by ventral and dorsal Basal Ganglia dopamine activity. J. Neurosci., October 18, 2006; 26(42): 10789 - 10795. [Abstract] [Full Text] [PDF]

				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]

				S. M. Berman, B. D. Naliboff, B. Suyenobu, J. S. Labus, J. Stains, J. A. Bueller, K. Ruby, and E. A. Mayer Sex differences in regional brain response to aversive pelvic visceral stimuli Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R268 - R276. [Abstract] [Full Text] [PDF]

				Y. R. Smith, C. S. Stohler, T. E. Nichols, J. A. Bueller, R. A. Koeppe, and J.-K. Zubieta Pronociceptive and Antinociceptive Effects of Estradiol through Endogenous Opioid Neurotransmission in Women J. Neurosci., May 24, 2006; 26(21): 5777 - 5785. [Abstract] [Full Text] [PDF]

				J C Kaski Cardiac syndrome X in women: the role of oestrogen deficiency Heart, May 1, 2006; 92(suppl_3): iii5 - iii9. [Abstract] [Full Text] [PDF]

				M. al'Absi, C. France, A. Harju, J. France, and L. Wittmers Adrenocortical and nociceptive responses to opioid blockade in hypertension-prone men and women. Psychosom Med, March 1, 2006; 68(2): 292 - 298. [Abstract] [Full Text] [PDF]

				F. Benedetti, H. S. Mayberg, T. D. Wager, C. S. Stohler, and J.-K. Zubieta Neurobiological Mechanisms of the Placebo Effect J. Neurosci., November 9, 2005; 25(45): 10390 - 10402. [Full Text] [PDF]

				J.-K. Zubieta, J. A. Bueller, L. R. Jackson, D. J. Scott, Y. Xu, R. A. Koeppe, T. E. Nichols, and C. S. Stohler Placebo Effects Mediated by Endogenous Opioid Activity on {micro}-Opioid Receptors J. Neurosci., August 24, 2005; 25(34): 7754 - 7762. [Abstract] [Full Text] [PDF]

				M. al'Absi, L. E. Wittmers, D. Ellestad, G. Nordehn, S. W. Kim, C. Kirschbaum, and J. E. Grant Sex Differences in Pain and Hypothalamic-Pituitary-Adrenocortical Responses to Opioid Blockade Psychosom Med, March 1, 2004; 66(2): 198 - 206. [Abstract] [Full Text] [PDF]

				J.-K. Zubieta, T. A. Ketter, J. A. Bueller, Y. Xu, M. R. Kilbourn, E. A. Young, and R. A. Koeppe Regulation of Human Affective Responses by Anterior Cingulate and Limbic {micro}-Opioid Neurotransmission Arch Gen Psychiatry, November 1, 2003; 60(11): 1145 - 1153. [Abstract] [Full Text] [PDF]

				J.-K. Zubieta, M. M. Heitzeg, Y. R. Smith, J. A. Bueller, K. Xu, Y. Xu, R. A. Koeppe, C. S. Stohler, and D. Goldman COMT val158met Genotype Affects {micro}-Opioid Neurotransmitter Responses to a Pain Stressor Science, February 21, 2003; 299(5610): 1240 - 1243. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help