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

Sadigh, Bita MD; Berglund, Margareta RN; Fillingim, Roger B. PhD; Sheps, David MD, PhD; Sylvén, Christer MD, PhD

doi: 10.1097/AJP.0b013e318154b974
Original Articles

Introduction 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.

Aims To study whether sex influences adenosine-provoked chest pain and the analgesic effect of the opioid receptor agonist β-endorphin.

Materials and Methods 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 β-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.

Results 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. β-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.

Conclusions In conclusion, women were resistant to β-endorphin modulation of adenosine-provoked chest pain. In male patients, β-endorphin induced analgesia.

Department of Cardiology, Karolinska Institute, Karolinska University Hospital-Huddinge, Stockholm, Sweden

Reprints: Bita Sadigh, MD, Department of Cardiology, Karolinska Institute, Karolinska University Hospital-Huddinge, 141 86 Stockholm, Sweden (e-mail:

Received for publication March 28, 2006; revised January 31, 2007; accepted June 16, 2007

© 2007 Lippincott Williams & Wilkins, Inc.