Modulation of musculoskeletal hyperalgesia by brown adipose tissue activity in mice

Elizabeth M.Goudie De Angelis, Ramy E. Abdelhamid, Myra G. Nunez, Casey L. Kissel, Katalin J. Kovács, Philip S. Portoghese, Alice A. Larson

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Cold exposure and a variety of types of mild stress increase pain in patients with painful disorders such as fibromyalgia syndrome. Acutely, stress induces thermogenesis by increasing sympathetic activation of beta-3 (β3) adrenergic receptors in brown adipose tissue. Chronic stress leads to the hypertrophy of brown adipose, a phenomenon termed adaptive thermogenesis. Based on the innervation of skeletal muscle by collaterals of nerves projecting to brown adipose, we theorized an association between brown adipose tissue activity and musculoskeletal hyperalgesia and tested this hypothesis in mice. Exposure to a cold swim or injection of BRL37344 (β3 adrenergic agonist) each enhanced musculoskeletal hyperalgesia, as indicated by morphine-sensitive decreases in grip force responses, whereas SR59230A (β3 adrenergic antagonist) attenuated swim-induced hyperalgesia. Chemical ablation of interscapular brown adipose, using Rose Bengal, attenuated the development of hyperalgesia in response to either swim stress or BRL37344. In addition, elimination of the gene expressing uncoupling protein-1 (UCP1), the enzyme responsible for thermogenesis, prevented musculoskeletal hyperalgesia in response to either a swim or BRL37344, as documented in UCP1-knockout (UCP1-KO) mice compared with wild-type controls. Together, these data provide a convergence of evidence suggesting that activation of brown adipose contributes to stress-induced musculoskeletal hyperalgesia.

Original languageEnglish (US)
Pages (from-to)2561-2570
Number of pages10
Issue number11
StatePublished - Aug 19 2016

Bibliographical note

Funding Information:
This work was supported by a grant from NIH from the National Institutes on Arthritis and Musculoskeletal and Skin Diseases [AR056092] and support from the College of Pharmacy and College of Veterinary Medicine at the University of Minnesota


  • Brown adipose tissue
  • Hyperalgesia
  • Pain
  • Stress
  • UCP1
  • β-adrenergic receptor


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