CCR2型
神经病理性疼痛
坐骨神经
小胶质细胞
医学
痛觉超敏
骨髓
内分泌学
痛觉过敏
麻醉
趋化因子
趋化因子受体
受体
伤害
病理
内科学
炎症
作者
Atsushi Sawada,Yukitoshi Niiyama,Koji Ataka,Kanna Nagaishi,Michiaki Yamakage,Mineko Fujimiya
出处
期刊:Pain
[Ovid Technologies (Wolters Kluwer)]
日期:2014-09-01
卷期号:155 (9): 1762-1772
被引量:68
标识
DOI:10.1016/j.pain.2014.05.031
摘要
Summary Bone marrow–derived microglia aggregated in the central nucleus of the amygdala are involved in the chronic neuropathic pain–induced anxiety. Chronic neuropathic pain causes abnormal sensitivities such as hyperalgesia and allodynia, and emotional abnormalities such as anxiety and depression. Although spinal cord microglia are involved in abnormal sensitivity to neuropathic pain, no previous studies have examined the mechanism of neuropathic pain–induced anxiety. Here, we examined the involvement of bone marrow (BM)–derived microglia aggregated in the amygdalae of mice with chronic neuropathic pain in the development of anxiety-like behavior. We prepared partial sciatic nerve ligations (PSNL) in mice that received bone marrow transplantation from green fluorescent protein (GFP)–Tg mice after irradiation with head protection, and examined GFP-positive microglia in the central nuclei of the amygdalae (CeA). On day 28 after PSNL, BM-derived microglia aggregated in the CeA concurrent with anxiety-like behavior. BM-derived microglia in the CeA highly expressed interleukin (IL)–1β and C-C chemokine receptor type 2 (CCR2). In addition, neurons in the CeA highly expressed monocyte chemotactic protein–1 (MCP-1), a ligand for CCR2, in PSNL-treated mice compared to sham-operated mice, suggesting that the MCP-1/CCR2 axis is involved in the recruitment of BM-derived microglia. Oral administration of a CCR2 antagonist decreased the number of BM-derived microglia in the CeA, and successfully reversed the anxiety-like behavior and hypersensitivity to mechanical stimuli in PSNL-treated mice. Microinjections of an IL-1β receptor antagonist directly into the CeA successfully reversed the anxiety-like behavior in the PSNL-treated mice even though the neuropathic pain persisted. These results suggest that the recruitment of BM-derived microglia to the CeA via the MCP-1/CCR2 axis and neuron–microglia interactions might be important in the pathogenesis of neuropathic pain–induced anxiety.
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