Chronic mu-opioid receptor stimulation in humans decreases muscle sympathetic nerve activity

Background-Opioid-addicted patients undergoing detoxification provide a uni que opportunity to assess the effects of chronic opioid receptor stimulatio n 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 mu -opioid receptor blockade during antagonist-supported detoxification under general anesthesia. Methods and Results-Fifteen young patients (30+/-1 years old, mean+/-SEM) w ith a long history of mono-opioid addiction and under oral methadone substi tution therapy (65+/-10 mg/d for 21+/-6 months) were selected. Peroneal MSA (microneurography) and catecholamine plasma concentrations thigh-performan ce liquid chromatography) were assessed in the awake state and compared wit h those of age-matched healthy control subjects. The effects of mu -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 conc entration (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/m in) 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/m in). Conclusions-Chronic <mu>-opioid receptor stimulation by methadone decreases resting MSA in humans.