Effects of Naltrexone on Pain Sensitivity and Mood in Fibromyalgia: No Evidence for Endogenous Opioid Pathophysiology

Abstract

The pathophysiological mechanisms underlying fibromyalgia are still unknown, although some evidence points to endogenous opioid dysfunction. We examined how endogenous opioid antagonism affects pain and mood for women with and without fibromyalgia. Ten women with fibromyalgia and ten age- and gender-matched, healthy controls each attended two laboratory sessions. Each participant received naltrexone (50mg) at one session, and placebo at the other session, in a randomized and double-blind fashion. Participants were tested for changes in sensitivity to heat, cold, and mechanical pain. Additionally, we collected measures of mood and opioid withdrawal symptoms during the laboratory sessions and at home the night following each session. At baseline, the fibromyalgia group exhibited more somatic complaints, greater sensory sensitivity, more opioid withdrawal somatic symptoms, and lower mechanical and cold pain-tolerance than did the healthy control group. Neither group experienced changes in pain sensitivity due to naltrexone administration. Naltrexone did not differentially affect self-reported withdrawal symptoms, or mood, in the fibromyalgia and control groups. Consistent with prior research, there was no evidence found for abnormal endogenous opioid activity in women with fibromyalgia.

Endogenous opioidergic dysregulation of pain in fibromyalgia: a PET and fMRI study

“…In a series of studies, Younger et al demonstrated analgesic effects of low dose naltrexone treatment in opioid-naïve FM patients. 66; 67 While these authors propose a different mechanism whereby low dose naltrexone acts to inhibit glial activation, we propose that low dose naltrexone could also increase MOR BP and consequently increase brain responses to endogenous opioid release. This latter hypothesis is consistent with early observations by Levine et al 41 wherein low dose naltrexone was shown to be analgesic only in responders to placebo, a process linked to increased MOR binding, 68 but not in placebo non-responders.…”

Regulation of Spinal Dynorphin 1-17 Release by Endogenous Pituitary Adenylyl Cyclase-Activating Polypeptide in the Male Rat: Relevance of Excitation via Disinhibition

“…The demonstrated activation of spinal Dyn-ergic neurons by disinhibition suggests that they function as a high-gain antinociceptive system that is kept in reserve. Given numerous reports of the inability of opioid receptor blockade to lower nociceptive response thresholds and induce nociception (El-Sobky et al, 1976;Grevert and Goldstein, 1978;Robertson et al, 2008;Younger et al, 2009), it is widely accepted that endogenous opioid-ergic neurons are normally quiescent. The current study provides an expanded understanding of basal opioid-ergic activity.…”

Mechanisms of Exercise-Induced Hypoalgesia

“…Participants then received an oral dose of either the opioid antagonist (50 mg naltrexone capsule) or a placebo (lactose capsule). Naltrexone (NAL) is an opioid receptor antagonist with particular affinity for µ-Opioid receptors 79 which are found both in the central and peripheral nervous system 14 The endogenous ligand with the highest affinity to the µ-opioid receptor is β-endorphin. 58 The order of placebo and NAL capsules were randomly assigned and administered in a double-blind fashion.…”