Opposite effects of opioid blockade on the blood pressure–pain relationship in depressed and non-depressed participants

Abstract

The effect of the opioid antagonist naltrexone on the relationship between blood pressure and pain was examined in 24 participants with major depressive disorder and 31 non-depressed controls, before and after 25 min of stressful mental arithmetic. Pain was induced by immersing the non-dominant foot in 2 °C ice-water for as long as possible or until 4 min had elapsed (the cold pressor test). Blood pressure was measured before each cold pressor test, and at 2-min intervals during mental arithmetic. In the group as a whole, neither depression nor naltrexone influenced blood pressure at any stage of the experiment. However, naltrexone disrupted an association between elevated resting blood pressure and low levels of pain in non-depressed controls, suggesting that endogenous opioid peptides are involved in blood pressure-mediated analgesia. Effects were similar when expressed in relation to blood pressure during psychological stress. In contrast to controls, blood pressure was unrelated to pain in depressed participants in the placebo condition. However, naltrexone unmasked an association between blood pressure and pain – those with highest blood pressure reported least cold-induced pain. Thus, endogenous opioids apparently masked an analgesic mechanism linking elevated blood pressure with reduced sensitivity to pain in participants with major depressive disorder. Noradrenergic mechanisms involved in active coping, stress-induced analgesia and baroreflexes might account for these findings.