New research indicates that a disruption of brain signals for reward and punishment contributes to increased pain sensitivity, known as hyperalgesia, in fibromyalgia patients. Results published in Arthritis & Rheumatism, a journal of the American College of Rheumatology, suggest that this altered brain processing might contribute to widespread pain and lack of response to opioid therapy in patients with fibromyalgia.
Fibromyalgia is a chronic, musculoskeletal syndrome characterized by widespread joint and muscle pain along with other symptoms such as fatigue, sleep disturbances, and cognitive difficulty. Previous research estimates that fibromyalgia affects 3.4% of women and 0.5% of men in the U.S. Prevalence of this pain disorder increases with age, affecting more than 7% of women between 60 and 79 years of age.
“In patients with fibromyalgia there is an alteration in the central nervous system pain processing and a poor response to topical pain treatments, trigger point injections and opioids,” said lead author Dr. Marco Loggia from Massachusetts General Hospital and Harvard Medical School in Boston. “Our study examines the disruption of brain function involved in the individual experience of pain anticipation and pain relief.”
For the present study, the research team enrolled 31 patients with fibromyalgia and 14 healthy controls. Functional magnetic resonance imaging (MRI) and cuff pressure pain stimuli on the leg were performed on all subjects. During the MRI, participants received visual cues alerting them of impending pain onset (pain anticipation) and pain offset (relief anticipation).
Results show that during pain anticipation and relief, fibromyalgia patients displayed less robust response within brain regions involved in sensory, affective, cognitive and pain regulating processes. The ventral tegmental area (VTA)—a group of neurons in the center of the brain involved in the processing of reward and punishment—displayed activation during pain anticipation and stimulation, but deactivation during anticipation of relief in healthy controls. In contrast, VTA responses during periods of pain, and anticipation of pain and relief, in fibromyalgia patients were significantly reduced or inhibited.
Dr. Loggia concludes, “Our findings suggest that fibromyalgia patients exhibit altered brain responses to punishing and rewarding events, such as expectancy of pain and relief of pain. These observations may contribute to explain the heightened sensitivity to pain, as well as the lack of effectiveness of pain medications such as opioids, observed in these patients. Future studies should further investigate the neurochemical basis underlying these dysfunctions.”
This research was supported by the National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health (NIH) grants (R01-AT004714, P01- AT002048, P01-AT006663, R01-AT005280; R01-AG034982, R21-AR057920).
Disrupted brain circuitry for pain-related reward/punishment in fibromyalgia
By Marco L. Loggia PhD, et al.
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OBJECTIVE: While patients suffering from fibromyalgia (FM) are known to exhibit hyperalgesia, the central mechanisms contributing to this altered pain processing are not fully understood. In this study we investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain such as anticipation of pain and of pain relief.
METHODS: FMRI was performed on 31 FM patients and 14 controls while they received cuff pressure pain stimuli on their leg, calibrated to elicit a pain rating of ~50/100. During the scan, subjects also received visual cues informing them of impending pain onset (pain anticipation) and pain offset (relief anticipation).
RESULTS: Patients exhibited less robust activations during both anticipation of pain and anticipation of relief within regions commonly thought to be involved in sensory, affective, cognitive and pain-modulatory processes.
In healthy controls, direct searches and region-of-interest analyses in the ventral tegmental area (VTA) revealed a pattern of activity compatible with the encoding of punishment: activation during pain anticipation and pain stimulation, but deactivation during relief anticipation.
In FM patients, however, VTA activity during pain and anticipation (of both pain and relief) periods was dramatically reduced or abolished.
CONCLUSION: FM patients exhibit disrupted brain responses to reward/punishment. The VTA is a source for reward-linked dopaminergic/GABAergic neurotransmission in the brain and our observations are compatible with reports of altered dopaminergic/GABAergic neurotransmission in FM. Reduced reward/punishment signaling in FM may relate to the augmented central processing of pain and reduced efficacy of opioid treatments in these patients.
© 2013 American College of Rheumatology.
Arthritis & Rheumatism. Wiley press release. November 5, 2013.
Arthritis & Rheumatism, November 7, 2013. By Marco L. Loggia PhD, Chantal Berna MD, PhD, Jieun Kim PhD, Christine M. Cahalan, Randy L. Gollub MD, PhD, Ajay D. Wasan MD, MSc, Richard E. Harris, Robert R. Edwards PhD, and Vitaly Napadow PhD. MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA.
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