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Psychosomatic Medicine 66:198-206 (2004)
© 2004 American Psychosomatic Society


ORIGINAL ARTICLES

Sex Differences in Pain and Hypothalamic-Pituitary-Adrenocortical Responses to Opioid Blockade

Mustafa al’Absi, PhD, Lorentz E. Wittmers, MD, PhD, Deanna Ellestad, RN, Glenn Nordehn, DO, Suck Won Kim, MD, Clemens Kirschbaum, PhD and Jon E. Grant, MD

From the Departments of Behavioral Sciences (M.A., D.E.), Family Medicine (M.A., G.N.), and Physiology (M.A., L.E.W.), University of Minnesota School of Medicine, Duluth, Minnesota; Department of Psychiatry (S.W.K., J.E.G.), University of Minnesota, Minneapolis, Minnesota; and Experimental Psychology (C.K.), University of Düsseldorf, Germany.

Address correspondence and reprint requests to Mustafa al’Absi, PhD, Department of Behavioral Sciences, University of Minnesota School of Medicine, Duluth, MN 55812. E-mail: malabsi{at}umn.edu

OBJECTIVE: Sex differences in pain sensitivity and stress reactivity have been well documented. Little is known about the role of the endogenous opioid system in these differences. This study was conducted to compare adrenocortical, pain sensitivity, and blood pressure responses to opioid blockade using naltrexone in men and women.

METHODS: Twenty-six participants completed 2 sessions during which placebo or 50 mg of naltrexone was administered, using a double-blind, counterbalanced design. Thermal pain threshold and heat tolerance were assessed. Participants also rated pain during a 90-second cold pressor test (CPT) and completed the McGill Pain Questionnaire (MPQ) after each pain challenge. Blood and saliva samples and cardiovascular and mood measures were obtained throughout the sessions.

RESULTS: Plasma cortisol, adrenocorticotropin, beta endorphin, prolactin, and salivary cortisol levels increased similarly in men and women after naltrexone administration compared with placebo. Women reported more pain during both pain procedures and had lower thermal pain tolerance. In response to naltrexone, women exhibited reduced blood pressure responses and reduced MPQ pain ratings after CPT. No effects of naltrexone on these measures were found in men.

CONCLUSIONS: Although men and women exhibited similar hormonal responses to opioid receptor blockade, women reported less pain and showed smaller blood pressure responses during CPT. Results suggest differential effects of the endogenous opioid system on pain perception and blood pressure in men and women.

Key Words: pain, • stress, • gender differences, • cortisol, • adrenocorticotropin, • naltrexone.

Abbreviations: CPT = cold pressor test;; HPA = hypothalamic–pituitary–adrenocortical;; HR = heart rate;; MPQ = McGill Pain Questionnaire;; SV = stroke volume.




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