Naltrexone effect on physiological and subjective response to a cold pressor task

Abstract

In this double-blind, cross-over study physiological (i.e. blood pressure, heart rate, plasma catecholamine concentrations, plasma cortisol concentrations) and subjective (i.e. McGill Pain Questionnaire, positive affect, distress) response to a cold pressor task was assessed in 19 subjects 1 h after the administration of 50 mg naltrexone and after placebo. Significant differences in plasma catecholamine concentrations were found. Plasma epinephrine concentrations increased during the 1 h period after naltrexone administration but remained largely unchanged after placebo administration. A significant treatment × period effect was also found for plasma norepinephrine concentrations. No significant differences were found for other measures assessed. Further research is necessary to determine the subpopulations in which these effects are of greatest magnitude and the long term safety implications of these effects.

Introduction

When one is subjected to a stressor, activation of the sympathetic system and the HPA axis occurs (Strike and Steptoe, 2003, Velasco et al., 1997). The magnitude of response to stressors has been studied as it relates to areas including cardiovascular disease and substance abuse (al’Absi, 2006, Sinha et al., 2006, Treiber et al., 2003). To more fully understand mechanisms by which stress response influences disease outcomes, it is important to study the various pathways by which stress response is regulated, of which the endogenous opioid system is one.

Opioid receptor antagonists are being studied in the treatment of substance use disorders (e.g. alcohol dependence, nicotine dependence, opioid abuse) (O’Malley et al., 2006, Roozen et al., 2006) and impulse control disorders (e.g. pathological gambling) (Kim et al., 2001). As use of these agents increases, more fully understanding their neuroendocrine effects is necessary. Since the endogenous opioid system is involved in the regulatory response to physiological and pain stressors, evaluation of opioid antagonists needs to be conducted both under resting and stress conditions. Additionally, testing the neuroendocrine and sympathetic response of opioid antagonists during stress can increase understanding of the endogenous opioid system in modulating stress response.

The goal of the described study is to evaluate the effect of naltrexone, an opioid antagonist, on cardiovascular response (i.e. blood pressure, heart rate, plasma catecholamine concentrations), neuroendocrine response (i.e. plasma cortisol concentrations), pain and distress measures during a cold pressor task. We hypothesized that opioid blockade would reverse the expected effects of endogenous opioids leading to an enhanced cardiovascular and neuroendocrine response and increased pain response.