Review of overlap between thermoregulation and pain modulation in fibromyalgia.

Fibromyalgia (FM) syndrome is characterized by widespread pain that is exacerbated by cold and stress but relieved by warmth. We review the points along thermal and pain pathways where temperature may influence pain. We also present evidence addressing the possibility that brown adipose tissue activity is linked to the pain of FM given that cold initiates thermogenesis in brown adipose tissue through adrenergic activity, whereas warmth suspends thermogenesis. Although females have a higher incidence of FM and more resting thermogenesis, they are less able to recruit brown adipose tissue in response to chronic stress than males. In addition, conditions that are frequently comorbid with FM compromise brown adipose activity making it less responsive to sympathetic stimulation. This results in lower body temperatures, lower metabolic rates, and lower circulating cortisol/corticosterone in response to stress--characteristics of FM. In the periphery, sympathetic nerves to brown adipose also project to surrounding tissues, including tender points characterizing FM. As a result, the musculoskeletal hyperalgesia associated with conditions such as FM may result from referred pain in the adjacent muscle and skin.