Opioid Resistance in Fibromyalgia Explained by Receptor Function

ANN ARBOR, Mich., Sept. 27 -- The reason that opioids seem to fizzle for fibromyalgia may be because of reduced receptor activity in regions of the brain that process and dampen pain signals, researchers here found.
Reduced µ-opioid receptor-binding potential in fibromyalgia patients was also significantly correlated with depression and emotional components of pain, reported Richard E. Harris, Ph.D., of the University of Michigan, and colleagues, in the Sept. 12 issue of the Journal of Neuroscience.
"Because these receptors are the target of opiate drugs," they wrote, "a profound reduction in the concentration or function of these receptors is consistent with a poor response of fibromyalgia patients to this class of analgesics, observed anecdotally in clinical settings."
The researchers used PET with a selective µ-opioid receptor radiotracer to assess receptor availability differences between fibromyalgia patients and healthy pain-free individuals.
Their study included 17 right-handed women with fibromyalgia (mean age 44.8, mean diagnosis duration 8.4 years) and 17 age- and sex-matched healthy controls who were part of an ongoing study of acupuncture treatment. The analysis was done on PET scans and other data collected at baseline.
No participants were taking opioids or had a history of their use. Of the 17 fibromyalgia patients, 10 were taking antidepressant medication, either serotonin reuptake inhibitors or dual serotonin/norepinephrine reuptake inhibitors.
The women reported "sensory" and "affective" characteristics of their pain on the Short Form of the McGill Pain Questionnaire immediately prior to undergoing the PET scan.
Depressive symptoms were self-reported on the Center for Epidemiological Studies-Depression Scale, which is used to detect major or clinical depression.
The PET scans showed significantly less opioid receptor-binding potential overall in fibromyalgia patients than in controls (P<0.01).
Fibromyalgia patients also had significantly less opioid receptor availability in four specific regions of the brain, the left and right nucleus accumbens, the left amygdala, and the right dorsal anterior cingulate (all P<0.05).
After controlling for global opioid receptor binding potential, the difference was still significant for the left (P<0.001) and right (P<0.05) nucleus accumbens and the amygdala (P<0.005). Activity in the dorsal anterior cingulate showed a similar trend (P<0.07).
"All of these regions have previously been noted to play some role in nociception and pain," Dr. Harris and colleagues said.
But, antidepressant use in the fibromyalgia group did not explain the opioid receptor abnormalities, the researchers said.
Binding potential in these four brain regions was not significantly different in fibromyalgia patients taking serotonin reuptake inhibitors or dual serotonin/norepinephrine reuptake inhibitors than among those not taking drugs in this class (all P>0.35).
Fibromyalgia patients also showed more depressive symptoms (P<0.05) with reduced opioid receptor binding within the amygdala, a region of the brain thought to modulate mood and the emotional dimension of pain.
Among fibromyalgia patients, reductions in opioid receptor-binding in the left nucleus accumbens was correlated with significant increases in the emotional component of clinical pain (P<0.05)>0.50). Controlling for antidepressant medication use did not change the association.
The relative amount of emotional versus sensory pain varied between patients in correlation with differences in opioid receptor binding in the dorsal anterior cingulate (P<0.05), posterior cingulate (P<0.001), and right ventral putamen (P<0.05) with a trend for the anterior cingulate (P=0.09).
"These results suggest that in fibromyalgia patients the affective quality of pain is associated with reduced µ-opioid receptor availability throughout the cingulate and other brain regions commonly associated with pain modulation," the researchers wrote.
Alterations in central opioid neurotransmission in specific brain regions "suggest that these mechanisms, possibly as a consequence of persistent pain, are involved in the clinical presentation and even the perpetuation of symptoms in this illness," they added.
Regardless of whether the mechanism is high endogenous opioids or downregulation of opioid receptors, the findings predict a poorer response to opioid painkillers for fibromyalgia patients, they concluded.
The study was supported by grants from the Department of Army, the National Institutes of Health. Dr. Harris was supported by a National Center for Complementary and Alternative Medicine grant and another researcher was likewise supported by a National Institutes of Health grant. None of the researchers reported conflicts of interest. Primary source: The Journal of NeuroscienceSource reference: Harris RE, et al "Decreased Central µ-Opioid Receptor Availability in Fibromyalgia" J Neurosci 2007;27:10000-10006.