title: Modulation of musculoskeletal hyperalgesia by brown adipose tissue activity in mice.
abstract: 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.
authors.affiliation: Departments of Veterinary and Biomedical Sciences and.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Goudie-DeAngelis
authors.affiliation: Departments of Veterinary and Biomedical Sciences and.
authors.forename: Ramy E
authors.initials: RE
authors.lastname: Abdelhamid
authors.affiliation: Departments of Veterinary and Biomedical Sciences and.
authors.forename: Myra G
authors.initials: MG
authors.lastname: Nunez
authors.affiliation: Departments of Veterinary and Biomedical Sciences and.
authors.forename: Casey L
authors.initials: CL
authors.lastname: Kissel
authors.affiliation: Departments of Veterinary and Biomedical Sciences and.
authors.forename: Katalin J
authors.initials: KJ
authors.lastname: Kovács
authors.affiliation: Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Portoghese
authors.affiliation: Departments of Veterinary and Biomedical Sciences and.
authors.forename: Alice A
authors.initials: AA
authors.lastname: Larson
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000473:pathology*; D000318:Adrenergic beta-Agonists / Q000633:toxicity; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000235:genetics; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D003080:Cold Temperature / Q000009:adverse effects; D004195:Disease Models, Animal; D004983:Ethanolamines / Q000633:toxicity; D005260:Female; D006930:Hyperalgesia / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053580:Muscle Strength / Q000187:drug effects; D059352:Musculoskeletal Pain / Q000150:complications* / Q000473:pathology / Q000601:surgery; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013550:Swimming / Q000523:psychology; D013623:Tail / Q000294:innervation; D000071256:Uncoupling Protein 1 / Q000172:deficiency / Q000235:genetics
chemical_list: D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C057368:BRL 37344