Peripheral macrophages contribute to nociceptor priming in mice with chronic intermittent hypoxia

IF 6.7 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Science Signaling Pub Date : 2024-07-30 DOI:10.1126/scisignal.adn8936

Samuel B. Chivers, Mary Ann Andrade, Robert J. Hammack, John Shannonhouse, Ruben Gomez, Yan Zhang, Brian Nguyen, Pankil Shah, Yu Shin Kim, Glenn M. Toney, Nathaniel A. Jeske

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Abstract

Obstructive sleep apnea (OSA) is a prevalent sleep disorder that is associated with increased incidence of chronic musculoskeletal pain. We investigated the mechanism of this association in a mouse model of chronic intermittent hypoxia (CIH) that mimics the repetitive hypoxemias of OSA. After 14 days of CIH, both male and female mice exhibited behaviors indicative of persistent pain, with biochemical markers in the spinal cord dorsal horn and sensory neurons of the dorsal root ganglia consistent with hyperalgesic priming. CIH, but not sleep fragmentation alone, induced an increase in macrophage recruitment to peripheral sensory tissues (sciatic nerve and dorsal root ganglia), an increase in inflammatory cytokines in the circulation, and nociceptor sensitization. Peripheral macrophage ablation blocked CIH-induced hyperalgesic priming. The findings suggest that correcting the hypoxia or targeting macrophage signaling might suppress persistent pain in patients with OSA.

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外周巨噬细胞有助于慢性间歇性缺氧小鼠的痛觉感受器启动。

阻塞性睡眠呼吸暂停（OSA）是一种普遍存在的睡眠障碍，与慢性肌肉骨骼疼痛的发病率增加有关。我们通过模拟 OSA 重复性低氧血症的慢性间歇性缺氧（CIH）小鼠模型研究了这种关联的机制。CIH 14 天后，雄性和雌性小鼠都表现出持续性疼痛的行为，脊髓背角和背根神经节感觉神经元的生化标记与痛觉亢进引物一致。CIH（而不是单独的睡眠破碎）会诱导巨噬细胞向外周感觉组织（坐骨神经和背根神经节）的招募增加、循环中的炎性细胞因子增加以及痛觉感受器敏感化。外周巨噬细胞消融阻断了CIH诱导的痛觉唤起。研究结果表明，纠正缺氧或针对巨噬细胞信号传导可能会抑制 OSA 患者的持续性疼痛。

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来源期刊

Science Signaling BIOCHEMISTRY & MOLECULAR BIOLOGY-CELL BIOLOGY

CiteScore

9.50

自引率

0.00%

发文量

148

审稿时长

3-8 weeks

期刊介绍： "Science Signaling" is a reputable, peer-reviewed journal dedicated to the exploration of cell communication mechanisms, offering a comprehensive view of the intricate processes that govern cellular regulation. This journal, published weekly online by the American Association for the Advancement of Science (AAAS), is a go-to resource for the latest research in cell signaling and its various facets. The journal's scope encompasses a broad range of topics, including the study of signaling networks, synthetic biology, systems biology, and the application of these findings in drug discovery. It also delves into the computational and modeling aspects of regulatory pathways, providing insights into how cells communicate and respond to their environment. In addition to publishing full-length articles that report on groundbreaking research, "Science Signaling" also features reviews that synthesize current knowledge in the field, focus articles that highlight specific areas of interest, and editor-written highlights that draw attention to particularly significant studies. This mix of content ensures that the journal serves as a valuable resource for both researchers and professionals looking to stay abreast of the latest advancements in cell communication science.