Hypertension-Associated Hypalgesia: Evidence in Experimental Animals and Humans, Pathophysiological Mechanisms, and Potential Clinical Consequences

Abstract

A behavioral hypalgesia (increased response threshold to noxious stimuli) has been consistently, although not invariably, reported in spontaneous and experimental acute and chronic hypertension in the rat. Studies in human hypertension have also demonstrated a diminished perception of pain, assessed as pain thresholds or ratings. The sensitivity to painful stimuli correlated inversely with blood pressure levels, and this relationship extended into the normotensive range. Evidence in humans and rats points to a role of the baroreflex system in modulating nociception. In the rat, blood pressure–related antinociception may be due to attenuated transmission of noxious stimuli at the spinal level secondary to descending inhibitory influences that are projected from brain stem sites involved in cardiovascular regulation and that may depend on baroreceptor activation and/or on a central “drive.” Both endorphinergic and noradrenergic central neurons (the latter acting through postsynaptic α 2 -receptors) have been shown to be involved, and other mediators probably also play a role. Functionally, blood pressure–related antinociception may represent an aspect of a more-complex coordinated adaptive response of the body to “stressful” situations. It is still uncertain whether in human essential hypertension hypalgesia is secondary to elevated blood pressure or whether both depend on some common mechanism. Studies on the effect of hypotensive treatment are too few to allow conclusions. According to one hypothesis, the reduction in pain perception caused by baroreceptor activation secondary to blood pressure elevation may represent a rewarding mechanism that may be reinforced with repeated stress and may be involved in the development of hypertension in some individuals. Hypertension-associated hypalgesia may have clinically relevant consequences, especially in silent myocardial ischemia and unrecognized myocardial infarction, both of which are more prevalent in hypertensive individuals.