Endogenous opioid system modulation in anginal pain: Demonstration of its central activity

Abstract

Plasma β-endorphin levels provide controversial results on the role of endogenous opioid system in modulation of anginal pain. As an alternative, the action of plasmatic luteinizing hormone after administration of naloxone was investigated: naloxone blocks the tonic endogenous opioid system inhibition of gonadotropin release; thus, the level of luteinizing hormone after naloxone administration is an index of central endogenous opioid system activity. Twenty patients with coronary artery disease and positive results of stress tests were selected: 10 had angina (group I) and 10 did not (group II). Ten healthy subjects were also studied as a control group (group III). In all patients basal plasma β-endorphin levels, basal luteinizing hormone plasma levels (every 15 minutes for 1 hour) and luteinizing hormone plasma levels after administration of 0.1 mg/kg naloxone over 4 minutes (every 15 minutes for 2 hours) were determined. In 15 patients the test was performed after luteinizing hormone releasing hormone was given. The integral concentration time of luteinizing hormone plasma level during baseline (LHiB) and after administration of naloxone (LHiN) or luteinizing hormone releasing hormone (LHiRH), the ratio (LHiN:LHiB and LHiRH:LHiB) and the differences (LHiN-LHiB and LHiRH − LHiB) between the postinfusion period and baseline were calculated. No difference was found in β-endorphin plasma levels and luteinizing hormone response after luteinizing hormone releasing hormone infusion. On the contrary, after naloxone administration, group II showed significantly higher responses (LHiN − LHiB, 2413 ± 380 mlU/ml; LHiN:LHiB, 5 ± 0.4) with respect to group I (LHiN − LHiB, 1150 ± 304 mlU/ml; p < 0.001; LHiN:LHiB, 2.7 ± 0.6; p < 0.001) and to group III (LHiN − LHiB, 1048 ± 279 mlU/ml; p < 0.001; LHiN:LHiB, 2.6 ± 0.4, p < 0.001). In comparison with β-endorphin levels, luteinizing hormone response to naloxone provides a better discrimination between patients with symptoms and those without symptoms, which demonstrates the role of the endogenous opioid system in modulating anginal pain.