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Modulation of musculoskeletal hyperalgesia by brown adipose tissue activity in mice

机译：小鼠棕色脂肪组织活性对肌肉骨骼痛觉过敏的调节

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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 (beta(3)) 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 (beta(3) adrenergic agonist) each enhanced musculoskeletal hyperalgesia, as indicated by morphine-sensitive decreases in grip force responses, whereas SR59230A (beta(3) 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.
机译：寒冷暴露和各种类型的轻度压力会增加患有诸如纤维肌痛综合征等疼痛性疾病的患者的疼痛。急性地，压力通过增加棕色脂肪组织中β-3（β（3））肾上腺素能受体的交感神经激活来诱导生热。慢性应激会导致棕色脂肪肥大，这种现象称为适应性生热。基于骨骼肌的神经支配到棕色脂肪的神经支配，我们对棕色脂肪组织活性与肌肉骨骼痛觉过敏之间的联系进行了理论分析，并在小鼠中验证了这一假设。暴露于冷泳或注射BRL37344（β（3）肾上腺素能激动剂）均会增强肌肉骨骼痛觉过敏，如吗啡敏感的抓地力响应下降所表明，而SR59230A（β（3）肾上腺素能拮抗剂）减弱了游泳引起的痛觉过敏。使用玫瑰红对肩cap间棕色脂肪进行化学消融，可减轻因游泳压力或BRL37344引起的痛觉过敏。此外，消除UCP1敲除（UCP1-KO）小鼠与野生动物相比，对游泳或BRL37344的反应，消除引起热生成的酶解表达蛋白1（UCP1）的基因可防止肌肉骨骼痛觉过敏。类型控件。总之，这些数据提供了证据，表明棕色脂肪的激活有助于应激诱导的肌肉骨骼痛觉过敏。

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