Fibromyalgia Brain Misreads Pleasure/Pain Signals

Janis C. Kelly

November 05, 2013

The widespread pain and lack of response to opioids in patients with fibromyalgia (FM) might be partly a result of mistakes in brain signals, according to an article published online November 5 in Arthritis & Rheumatism by Marco L. Loggia, PhD, and colleagues.

"While the neural responses to pain in [FM] have been the object of several investigations, potential dysregulation of the neural mechanisms underlying anticipation of pain and anticipation of pain relief in this chronic pain population has received little attention,," Dr. Loggia told Medscape Medical News. "We show that FM patients exhibit reduced brain activity in response to visual cues informing them of impending pain onset (pain anticipation) and pain offset (relief anticipation). This reduced responsiveness was seen in various regions, including regions involved in the processing of rewards/punishment. This is an interesting observation, given that several studies are suggesting a relationship between chronic pain and alterations in reward neurocircuitry." Dr. Loggia is instructor in radiology at Harvard Medical School and assistant in neuroscience at Massachusetts General Hospital, Boston.

When the investigators compared functional magnetic resonance imaging and cuff pressure pain stimuli in 31 patients with FM and in 14 healthy control participants, they found that the patients with FM lacked normal activation of the brain ventral tegmental area (VTA) during pain anticipation and deactivation of the VTA during anticipation of pain relief. During the imaging, participants received visual cues alerting them of impending pain onset (pain anticipation) and pain offset (relief anticipation).

Activation responses in patients with FM were also abnormal in the supplementary motor area, middle and posterior cingulate cortices, and periaqueductal gray, as well as in the caudate nucleus and globus pallidus on the left and in the second somatosensory cortex and posterior insula on the right.

The VTA is involved in the processing of reward and punishment. In healthy participants , the VTA is activated during anticipation of or actual experience of pain and is deactivated when relief is expected. In contrast, in patients with FM, VTA responses during periods of pain and in anticipation of pain and relief were significantly reduced or inhibited.

The VTA mediates reward-linked dopaminergic/GABAergic transmission, and the authors note that their data are compatible with other reports that this type of transmission is altered in FM.

Dr. Loggia said the researchers were quite surprised by the extent of the changes in brain function in FM. "While I did expect to observe reduced responses to the anticipatory cues in some regions (eg, the regions involved in the descending pain modulatory system, which is known to be altered in these patients), I did not expect to see so many regions exhibit this behavior. Now the question to investigate is what causes these alterations. We are now trying to investigate whether psychological factors can explain these results," he said.

The new findings also help explain another aspect of FM: lack of response to opioids. "Thus, reduced VTA response to pain (as well as pain anticipation/relief) in FM suggests that altered neurotransmission in this and similar reward/punishment processing brain regions might support the lack of therapeutic efficacy of opioids in treating FM pain (opioid use for management of pain in FM is in fact not recommended by any current guideline)," the authors write.

"I think the main message clinically is that there are prominent central changes in pain processing and that the preponderance of evidence is that this is a central nervous system disease," Daniel J. Clauw, MD, told Medscape Medical News. Dr. Clauw, who was not involved in this study, is professor of anesthesiology, medicine (rheumatology), and psychiatry and is also director of the Chronic Pain and Fatigue Research Center at the University of Michigan in Ann Arbor.

"A secondary message may be that this lends further support to the fact that GABAergic and dopaminergic mechanisms are playing a role in FM, but I think that type of hypothesis is best studied by showing that FM patients are responsive to drugs with those mechanisms of action (which have been done)," he continued.

Dr. Loggia said that another potential implication of these observations is that cognitive strategies aimed at changing the patient's expectations regarding pain relief and the outcome of therapy might be beneficial in FM.

The study was supported by the National Center for Complementary and Alternative Medicine. The authors and Dr. Clauw have disclosed no relevant financial relationships.

Arthritis Rheum. Published online November 5, 2013.

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