Changes in cardiac vagal tone as measured by heart rate variability during naloxone-induced opioid withdrawal

Abstract

BackgroundHeart rate variability (HRV) is of interest to researchers due to its potential utility as a marker for both physiological and psychological stress. Sympatholytics are used to treat opioid withdrawal, but little information about the parasympathetic system’s role in mediating withdrawal symptoms exists. The goal of the current study was to evaluate changes in HRV during opioid withdrawal to provide a better understanding of the autonomic effects of opioid withdrawal. MethodsTen male participants (mean age = 46.4 years) received intramuscular naloxone (mean dose =0.26 mg) to confirm opioid dependence. The presence and severity of withdrawal symptoms were assessed using subjective and objective measures (Wang et al., 1974). Electrocardiography (ECG) was measured continuously, and HRV was analyzed in 2-minute segments before naloxone injection (at baseline) and after participants were in moderate withdrawal (Wang Test score ≥10). Heart rate, blood pressure, pupil diameter, and respiratory rate were also examined. ResultsPupil diameter significantly increased after naloxone administration relative to baseline (t(9) = 5.562, p = 0.000). Both high frequency (HF) HRV (Z = -2.803, p = 0.005) and root mean square of successive differences (RMSSD) HRV (Z = -2.090, p = 0.037) were significantly lower during withdrawal relative to baseline. Increases in heart rate (Z = -2.090, p = 0.032) and systolic pressure (t(9) = 8.099, p = 0.0000) from baseline to withdrawal also were significant. ConclusionsThese preliminary data indicate that a large reduction in cardiac vagal tone occurs during naloxone-induced withdrawal. This finding underscores the need for further research into the role of the parasympathetic nervous system in opioid withdrawal.