Brown adipose tissue plays an important role in thermogenesis and metabolism in response to stress. Acutely, stress induces thermogenesis by increasing sympathetic tone to beta3 (β3) adrenergic receptors in brown adipose. Chronic stress leads to the hypertrophy of brown adipose, a phenomenon termed adaptive thermogenesis. Cold exposure and the associated sympathetic activity from a variety of stresses are also known to increase pain in patients suffering from painful disorders such as fibromyalgia syndrome. We theorized an association between brown adipose tissue activity and musculoskeletal hyperalgesia and tested this hypothesis in mice. Exposure to a cold swim stress enhanced musculoskeletal hyperalgesia, as indicated by morphine-sensitive decreases in grip force responses. Stimulation of β3 adrenergic receptors by injection of BRL37344, a β3 adrenergic agonist, also enhanced musculoskeletal hyperalgesia, consistent with the activation of the unique set of adrenergic receptors located in brown adipose. Chemical ablation of interscapular brown adipose, using Rose Bengal, attenuated the development of hyperalgesia in response to either swim stress or BRL37344. Similarly, elimination of the gene expressing uncoupling protein-1 (UCP1), the enzyme responsible for thermogenesis, prevented musculoskeletal hyperalgesia in response to a swim stress, as documented in UCP1-knock out (UCP1-KO) mice compared to wild type controls. Together these data provide a convergence of several lines of evidence suggesting that the acute activation of brown adipose contributes to muscloskeletal hyperalgesia. However, the baseline nociceptive sensitivity of UCP1-KO mice was greater than wild type controls, suggesting that a mechanism that promotes muscle pain is present that compensates for the absence of UCP1.
University of Minnesota M.S. thesis. August 2016. Major: Veterinary Medicine. Advisor: Alice Larson. 1 computer file (PDF); v, 28 pages.
Modulation of Musculoskeletal Hyperalgesia by Brown Adipose Tissue Activity in Mice.
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