Exposure to Cold Unmasks Potential Biomarkers of Fibromyalgia Syndrome Reflecting Insufficient Sympathetic Responses to Stress.

OBJECTIVES: Fibromyalgia syndrome (FMS) is a chronically painful condition whose symptoms are widely reported to be exacerbated by stress. We hypothesized that female patients with FMS differ from pain-free female controls in their sympathetic responses, a fact that may unmask important biomarkers and factors that contribute to the etiology of FMS. MATERIALS AND METHODS: In a pilot study, blood pressure (BP), skin temperature, thermogenic activity, circulating glucose, and pain sensitivity of 13 individuals with FMS and 11 controls at room temperature (24°C) were compared with that after exposure to cold (19°C). RESULTS: When measured at 24°C, BP, skin temperature, blood glucose, and brown adipose tissue (BAT) activity, measured using F-fluorodeoxyglucose positron-emission tomography/computed tomography, did not differ between controls and individuals with FMS. However, after cold exposure (19°C), BP and BAT activity increased in controls but not in individuals with FMS; skin temperature on the calf and arm decreased in controls more than in individiuals with FMS; and circulating glucose was lower in individiuals with FMS than in controls. Pain sensitivity did not change during the testing interval in response to cold. DISCUSSION: The convergence of the effect of cold on 4 relatively simple measures of thermogenic, cardiovascular, and metabolic activity, each regulated by sympathetic activity, strongly indicate that individuals with FMS have impaired sympathetic responses to stress that are observable and highly significant even when measured in extraordinarily small sample populations. If insufficient sympathetic responses to stress are linked to FMS, stress may unmask and maximize these potential clinical biomarkers of FMS and be related to its etiology.

Automated quantitation of cold-inducible human brown adipose tissue with FDG PET/CT with application to fibromyalgia.

Increasing recognition of the importance of brown adipose tissue (BAT) motivates the development of reproducible and quantitative methods for measuring it. Positron emission tomography (PET)/computerized tomography (CT) with 18F-fluorodeoxyglucose (FDG) has become the principal method to non-invasively detect brown adipose tissue (BAT) in humans. Improvements in quantitation and standardization will drive further clinical application. One disorder hypothesized to involve dysregulation in thermoregulation and the processing of pain involving BAT is fibromyalgia syndrome (FMS). This report describes an approach with additional technical standardization to measure cold-inducible, BAT activity (ci-BAT) semi-quantitatively and reliably with minimal operator intervention with the FDG PET/CT technique. Ci-BAT was measured to test whether FMS patients have decreased BAT activation compared to normal controls. Threshold parameters to optimally separate ci-BAT from non-ci-BAT were developed based on the distribution of the pixel-wise parametric data from each merged PET/CT scan for each study session occurring on different days. BAT activity was the same under warm conditions in both control and FMS subjects attesting to reproducibility and reliability. However, considerable variability arose between groups at cool temperatures consistent with other literature. Increases in ci-BAT activity were significantly less in FMS patients than in controls, as hypothesized. Ci-BAT recruitment can be quantified non-invasively using FDG PET/CT using semi-automated techniques in human subjects across different diagnostic groups or within groups undergoing manipulations of interest.