Effect of raised plasma beta endorphin concentrations on peripheral pain and angina thresholds in patients with stable angina

Abstract

Objective: To determine whether changes in plasma concentrations of beta endorphins alter angina threshold and peripheral pain threshold in patients with stable angina.

Design: Latin square design comparison of angina thresholds by exercise treadmill test and peripheral pain thresholds using a radiant heat source in eight patients with stable angina under control conditions, after stimulation of pituitary beta endorphin release by ketoconazole, after suppression of pituitary beta endorphin release by dexamethasone, and after blockade of opioid receptors by intravenous naloxone.

Results: An approximately fivefold increase in circulating concentrations of beta endorphins was found after administration of ketoconazole (mean (SEM): 13.9 (1.2) v 73.8 (6.2) pg/ml; p < 0.05), which was associated with an increase in peripheral pain threshold to a radiant heat source (time to onset of pain perception 72 (19) v 123 (40) seconds; p < 0.05), but no significant difference in angina threshold. A reduction in circulating concentrations of beta endorphins after pretreatment with dexamethasone was statistically non-significant (13.9 (1.2) v 9.0 (1.5) pg/ml; NS) and was not associated with any change in either peripheral pain or angina thresholds. No effects were seen after blockade of opioid receptors by previous administration of intravenous naloxone.

Conclusions: Increased plasma concentrations of beta endorphins alter peripheral pain threshold but not angina threshold in patients with stable angina pectoris.

Figure 1

Plasma concentrations of β endorphin, adrenocorticotrophic hormone (ACTH), and cortisol before, during, and at 10 and 20 minutes after treadmill exercise in eight patients with stable angina, under control conditions (filled circles), and after pretreatment with ketoconazole (empty circles), dexamethasone (filled triangles), or naloxone (empty triangles). Error bars are SEM.

Figure 2

Plasma β endorphin concentrations at onset of angina (upper panel), peripheral pain thresholds (middle panel), and anginal thresholds (lower panel) during exercise treadmill testing in eight patients under control conditions (C), and after pretreatment with ketoconazole (K), dexamethasone (D), and naloxone (N). Error bars are SEM.

Figure 3

Relation between changes in plasma β endorphin concentrations and changes in angina threshold (left panel) and peripheral pain threshold (right panel) from control after pretreatment with ketoconazole (K), dexamethasone (D), or naloxone (N). Error bars are SEM.