Effects of naloxone on hemodynamic and sympathetic nerve responses to pain in normotensive vs. borderline hypertensive men

Abstract

Pain sensitivity decreases with increasing resting blood pressure. This blood pressure–pain interaction may be mediated by endogenous opioids which have been shown to affect both blood pressure and nociception. To test this hypothesis, we measured mean arterial blood pressure (MAP), central venous pressure (CVP), heart rate (HR), muscle sympathetic nerve activity (MSNA), serum catecholamines, and individual pain rating scales during 2 min periods of noxious mechanostimulation (skin fold pinching) in nine young (26±2 year), male normotensive (NT) subjects and in 12 age and weight matched males with borderline hypertension (BHT). Measurements were performed before and after the i.v. administration of naloxone (0.15 mg/kg) and placebo in a randomized double-blind cross-over trial. In the pre-naloxone trials, pain led to similar changes in MAP, CVP, MSNA and plasma catecholamines in the two groups except for a higher increase in HR in the BHT group as compared to the NT group (3±1 vs. 1±1 bpm; P<0.005). Opioid blockade with naloxone increased MSNA responses to pain in the NT group (from 5±1 to 9±1 bursts/min, and, from 100±23 to 204±36 units/min, respectively; P<0.05) but did not significantly affect the MSNA response to pain in the BHT group. Pain induced responses of MAP, CVP, and catecholamines were not altered by naloxone in either group. Overall, there was a highly significant inverse correlation between pain perception and resting blood pressure which was not significantly affected by naloxone. The BHT subjects exhibited a lower pain perception compared to the NT subjects ( P<0.005). Naloxone increased pain rating in the NT group (from 194±9 to 218±13; P<0.005) but not in the borderline hypertensive group (160±8 vs. 168±10; P=0.36). Except for a decreased HR response in the BHT group, placebo had no effect on the responses to pain. Our data do not indicate a major role of the endogenous opioid system for the blood pressure–pain interaction in man. Endogenous opioids affect pain perception and sympathetic nerve activity responses to pain in normotensive men but their activity seems to be attenuated in borderline hypertensive subjects. Therefore, the lower pain sensitivity in human essential hypertension is probably mediated by non-opioid mechanisms.