Chronic μ-Opioid Receptor Stimulation in Humans Decreases Muscle Sympathetic Nerve Activity

Abstract

Background —Opioid-addicted patients undergoing detoxification provide a unique opportunity to assess the effects of chronic opioid receptor stimulation on the sympathetic nervous system. We tested the hypothesis that chronic oral methadone intake decreases resting efferent sympathetic nerve activity to muscle (MSA). Furthermore, we assessed whether this effect is reversed by μ-opioid receptor blockade during antagonist-supported detoxification under general anesthesia. Methods and Results —Fifteen young patients (30±1 years old, mean±SEM) with a long history of mono-opioid addiction and under oral methadone substitution therapy (65±10 mg/d for 21±6 months) were selected. Peroneal MSA (microneurography) and catecholamine plasma concentrations (high-performance liquid chromatography) were assessed in the awake state and compared with those of age-matched healthy control subjects. The effects of μ-opioid receptor blockade by naloxone (12.4 mg IV) were determined during propofol anesthesia. Compared with healthy volunteers, resting MSA (4±2 versus 22±2 bursts/min, P <0.0001) and antecubital venous norepinephrine plasma concentration (100±64 versus 256±48 pg/mL, P =0.01) were markedly decreased in addicted patients despite similar arterial blood pressure and heart rate. Opioid receptor blockade markedly increased MSA (5±2 to 24±3 bursts/min) and norepinephrine (49±12 to 305±48 pg/mL) and epinephrine (13±2 to 482±67 pg/mL) arterial plasma concentrations as well as mean arterial pressure (82±4 to 108±3 mm Hg) and heart rate (70±3 to 86±4 beats/min). Conclusions —Chronic μ-opioid receptor stimulation by methadone decreases resting MSA in humans.