Role of the central endogenous opiate system in patients with syndrome X

To evaluate the role of the endogenous opioid system (EOS) in abnormal pain perception in patients with syndrome X, we used a neuroendocrine approach, evaluating plasmatic luteinizing hormone (LH) changes after naloxone, a competitive antagonist of opioid receptors able to unblock tonic EOS inhibition on gonadotropin release. Thus LH response to naloxone test indicates the central EOS activity on hypothalamic luteinizing hormone-releasing hormone (LH-RH) inhibitory opioid receptors.

Ten patients with syndrome X, 10 age-matched male patients with coronary artery disease (CAD), and 10 normal subjects were analyzed. Naloxone tests were performed between 8 and 9 am. Basal beta-endorphin and LH levels were determined on 4 blood samples at 20-minute intervals; after naloxone (0.1 mg/kg intravenously in 4 minutes), LH was measured on 8 samples at 15-minute intervals. In all patients the test was also performed after LH-RH administration. Anginal pain on exercise testing was subjectively scored on a 1 to 10 analogic scale and wall motion abnormalities were quantified by a wall motion score index.

Significant differences were found in LH release after naloxone (CAD 260.3 +/- 42.6 vs syndrome X 151.6 +/- 48.5 mIU/mL, P <.05), angina score (CAD 5.5 +/- 1.3 vs syndrome X 7.2 +/- 1.7, P <.05), and wall motion abnormalities (CAD 3.6 +/- 1. 2 vs syndrome X 2.8 +/- 1.9, P <.05).

The reduced LH release after naloxone in syndrome X, with a normal LH-RH response, suggests a lower central EOS activity, which may be related to the higher anginal pain perception.