The majority of studies involving experimentally-induced pain have shown that women are more sensitive to pain than men. Unfortunately, many of the pain procedures that have found sex differences confound sensory (the ability to discriminate pain) and emotional (subjective reports of pain) variables by treating pain as a single dimension, when in fact pain varies along a range of dimensions. Further, while data suggest that sex differences in pain response may be related to circulating gonadal hormones, the definition and measurement of menstrual cycle phase has been inadequate. The purpose of the present application is to more fully investigate sex differences in response to painful stimuli, specifically focusing on 1) the influence of gonadal hormones on pain responsivity and 2) the analgesic response to mu (morphine) and kappa (butorphanol) opioid agonists. Each study will use two pain procedures: the cold pressor test, which combines sensory and emotional aspects of pain, and the mechanical pressure test, which yields data amenable to Signal Detection Theory analysis (i.e., can distinguish between sensory and emotional pain). Further, each study will compare normally-cycling women to women maintained on oral contraceptives and to men. Phase of the cycle will be verified via documentation of ovulation in normally-cycling women and hormone levels (estradiol and progesterone) in all participants. The first study will measure pain response at five different phases of the menstrual cycle (menstrual, follicular, ovulatory, luteal, and late luteal) in normally-cycling women; women on oral contraceptives and men will be tested during the same five """"""""phases."""""""" Studies 2 and 3 will compare the analgesic effect of butorphanol and morphine in the three groups across two menstrual-cycle phases (based on Study 1). A dose- response function for each drug will be obtained and blood samples will be collected to determine any pharmacokinetic differences across the three groups and cycle phases. These studies will provide important information regarding sex differences in analgesic response, which may be due to cyclical fluctuations in gonadal hormones. In addition, they will more carefully examine sex differences in analgesic response to butorphanol and morphine, two agonists with differing selectivities for mu and kappa opioid receptors.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
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Special Emphasis Panel (ZDE1-YS (16))
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New York State Psychiatric Institute
New York
United States
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Comer, Sandra D; Cooper, Ziva D; Kowalczyk, William J et al. (2010) Evaluation of potential sex differences in the subjective and analgesic effects of morphine in normal, healthy volunteers. Psychopharmacology (Berl) 208:45-55
Kowalczyk, William J; Evans, Suzette M; Bisaga, Adam M et al. (2006) Sex differences and hormonal influences on response to cold pressor pain in humans. J Pain 7:151-60