Opioid-induced hyperalgesia might explain pain in fibromyalgia patients

WASHINGTON — Strong associations between evoked pain activations in patients with fibromyalgia were suggestive of hyperalgesia and mu-opioid receptor availability, according to research presented at the American College of Rheumatology Annual Meeting.

“Over the last decade it’s become more and more clear that the pain in fibromyalgia is probably due to changes in the central nervous system, more specifically, alterations in the way the brain actually functions,” researcher Richard E. Harris, PhD, assistant professor in the department of anesthesiology, Chronic Pain & Fatigue Research Center at the University of Michigan, said. “This definitely makes sense for subjective symptoms such as pain.

Richard E. Harris

“We wanted to look at two factors and see if they were related in these patients. One factor was the response to evoked pain stimuli, that’s looking at the fMRI signal in response to pressure pain applied to the thumb, and the other imaging modality that we used was looking at opioid receptors … located throughout the central nervous system and the peripheral nervous system.”

Researchers studied 18 women with fibromyalgia who were opioid-naive. Nine nonpharmacological treatments were administered to patients during 4 weeks, with functional magnetic resonance imaging (fMRI) of varying levels applied to the thumb as well as a 90-minute [11C]carfentanil PET scan under resting conditions conducted at baseline and after treatments. Biological Parametric Mapping toolbox was used to analyze the whole-brain voxel-by-voxel correlation analysis between fMRI and PET difference images. A correlation coefficient defined activation clusters, with R≥0.6 uncorrected. Clinical pain was measured by Short Form McGill Pain Questionnaire (SFMPQ).

Multiple regions involved in pain processing and modulation displayed negative correlations between changes in the fMRI blood oxygenation level dependent (BOLD) signal and mu-opioid receptor (MOR) binding potential (BP). They included: right posterior insula (R=–0.82, P=.0004); left medial insula (R=–0.82, P=.0003); left orbital frontal cortex (R=–0.75, P=.0004); right amygdala (R=–0.68, P=.002): and brainstem (R=–.071, P=.0009). Right dorsolateral prefrontal cortex (DLPFC; R=0.66, P=.003); posterior cingulate (R=0.62, P=.006) and right putamen (R=0.72, P=.0008) displayed positive correlations.

Researchers noted that “changes in functional imaging outcomes were negatively associated with changes in clinical pain: BOLD in right DLPFC and clinical pain SFMPQ (R=–.052, P=.03); MOR BP in left medial insula and SFMPQ present pain (R=–0.51, P=.03).”

“The implications of this study are twofold,” Harris said. “One is that pain in fibromyalgia might actually be due to what we term endogenous opioid-induced hyperalgesia, where the overuse of the opiate system might cause a down regulation in the number of receptors. The other implication is that these patients who have changes in the opioid receptor system … we predict might be less likely to respond to classical exogenous opioids like morphine or codeine. However, that speculation needs to be framed in the context of the fact that we didn’t actually expose them to any drugs in the study.”

Disclosure: Dr. Harris and researcher Daniel J. Clauw, MD, reported numerous financial disclosures.

For more information:

Wang H. P2450: Evoked Pain Brain Response Is Associated with Reduced μ-Opioid Receptor Binding in Fibromyalgia. Presented at: American College of Rheumatology 2012 Annual Meeting; Nov. 10-14, Washington.