Much epidemiological, clinical, and experimental data attests to a relationship between gender and the perception of painful stimuli: women have greater pain sensitivity than men. In this research, the question is raised as to whether differences in opioid peptide responses are responsible, at least in part, for these gender differences. The investigators will examine gender differences in pain sensitivity in patients with stable angina, and in individuals without evidence of coronary artery disease and no chest pain. The following specific aims will be tested: (1) Women will exhibit greater sensitivity to thermal, ischemic, and cold pressor pain than men, and in men, but not women, pain sensitivity will be inversely related to plasma beta-endorphin levels; (2) Induction of chest pain by adenosine will be attenuated by beta-endorphin infusion in men, but not women, this effect will be reversed by naloxone; (3) Use of a cognitive strategy (imagery) will attenuate pain sensitivity, as indexed by tolerance and threshold to ischemic pain and time to onset of angina during exercise testing, to a greater extent in men and will be reversed by naloxone. In Study 1, 200 subjects will undergo cold pressor, forearm ischemia, and thermal pain tests in randomized order. Blood pressure, heart rate and plasma beta-endorphin levels will be determined to assess whether they mediate pain perception differently in men and women. In Study 2, the investigators plan to examine whether plasma beta-endorphin levels attenuate adenosine-provoked chest pain to a greater extent in men than women. The dose-effect curve for pain provoked by adenosine will be established for 40 subjects. Beta-endorphin, and later naloxone, will then be infused and a new dose-effect curve for adenosine-provoked chest pain will be established. In Study 3, they will examine whether cognitive coping strategies attenuate pain differently in men and women. 200 subjects will be assigned to one of two conditions: control and imagery task. Subjects will undergo an exercise test and forearm ischemia test in random order. Blood pressure, heart rate and plasma beta-endorphin levels will be determined to assess whether they mediate pain sensitivity differently in men and women. Finally, naloxone will be introduced to determine if thee effects are mediated by beta-endorphin.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Behavioral Medicine Study Section (BEM)
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University of Florida
Internal Medicine/Medicine
Schools of Medicine
United States
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Stewart, Jesse C; France, Christopher R; Sheffield, David (2003) Hypertension awareness and pain reports: data from the NHANES III. Ann Behav Med 26:8-14
Brown, Jennifer L; Sheffield, David; Leary, Mark R et al. (2003) Social support and experimental pain. Psychosom Med 65:276-83
Gupta, Vishal; Sheffield, David; Verne, G Nicholas (2002) Evidence for autonomic dysregulation in the irritable bowel syndrome. Dig Dis Sci 47:1716-22
Myers, C D; Robinson, M E; Riley 3rd, J L et al. (2001) Sex, gender, and blood pressure: contributions to experimental pain report. Psychosom Med 63:545-50