Disrupted Brain Circuitry for Pain-Related Reward/Punishment in Fibromyalgia

Objective. While patients with fibromyalgia (FM) are known to exhibit hyperalgesia, the central mechanisms contributing to this altered pain processing are not fully understood. This study was undertaken to investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain, such as anticipation of pain and anticipation of pain relief. Methods. Thirty-one FM patients and 14 controls underwent functional magnetic resonance imaging, while receiving cuff pressure pain stimuli on the leg calibrated to elicit a pain rating of similar to 50 on a 100-point scale. During the scan, subjects also received visual cues informing them of the impending onset of pain (pain anticipation) and the impending offset of pain (relief anticipation). Results. Patients exhibited less robust activation during both anticipation of pain and anticipation of relief within regions of the brain commonly thought to be involved in sensory, affective, cognitive, and painmodulatory processes. In healthy controls, direct searches and region-of-interest analyses of the ventral tegmental area revealed a pattern of activity compatible with the encoding of punishment signals: activation during anticipation of pain and pain stimulation, but deactivation during anticipation of pain relief. In FM patients, however, activity in the ventral tegmental area during periods of pain and periods of anticipation (of both pain and relief) was dramatically reduced or abolished. Conclusion. FM patients exhibit disrupted brain responses to reward/punishment. The ventral tegmental area is a source of reward-linked dopaminergic/gamma-aminobutyric acid-releasing (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 be related to the augmented central processing of pain and reduced efficacy of opioid treatments in these patients.