β-Endorphin Modulates Adenosine Provoked Chest Pain in Men, But Not in Women—A Comparison Between Patients With Ischemic Heart Disease and Healthy Volunteers

Abstract

Increasing evidence suggests the existence of sex differences in pain perception. Adenosine, an early messenger for myocardial ischemia induces angina pectorislike symptoms in healthy volunteers and in patients with ischemic heart disease. To study whether sex influences adenosine-provoked chest pain and the analgesic effect of the opioid receptor agonist beta-endorphin. Twenty patients (10 male and 10 female) with significant coronary artery disease and 20 healthy volunteers (10 male and 10 female) were studied. Both the hand algometer and Borg CR-10 scale were used to estimate chest pain. Chest pain was provoked double-blind by injections of placebo, 1/3, 2/3, 3/3 of maximal tolerable dose of adenosine twice in randomized order. This procedure was repeated after bolus injection of beta-endorphin followed by infusion and repeated a third time after bolus injection of naloxone 0.8 mg. Central chest pain and physiologic responses were quantified using hemodynamic and psychophysical methods. Pain estimate by hand algometer and the Borg CR-10 scale was correlated (r=0.77, P<0.001). Both sexes reported a dose-dependent increase of adenosine-provoked chest pain with no differences for maximum tolerable dose of adenosine per kilogram. beta-Endorphin administration lowered adenosine-provoked pain in both male patients and male healthy volunteers (P=0.02) but not in women. Naloxone tended to increase the pain perception in male patients (P=0.052) and male healthy volunteers (P=0.054), but did not have any significant effect on pain modalities in female. In conclusion, women were resistant to beta-endorphin modulation of adenosine-provoked chest pain. In male patients, beta-endorphin induced analgesia.