A spinal microglia population involved in remitting and relapsing neuropathic pain
A spinal microglia population involved in remitting and relapsing neuropathic pain
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DOI：
10.1126/science.abf6805
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发表时间：
2022-04-01
期刊：
影响因子：
56.9
通讯作者：
Tsuda, Makoto
中科院分区：
文献类型：
--
作者：
Kohno, Keita;Shirasaka, Ryoji;Tsuda, Makoto
神经性疼痛通常由影响躯体感觉系统的损伤和疾病引起。虽然疼痛的发展已经得到了很好的研究，但疼痛的恢复机制在很大程度上仍然未知。在这里，我们发现表达CD 11 c的脊髓小胶质细胞出现在神经损伤后行为疼痛超敏反应的发展之后。脊髓CD 11 c（+）小胶质细胞耗竭的神经损伤小鼠无法从这种超敏反应中自发恢复。CD 11 c（+）小胶质细胞表达胰岛素样生长因子-1（IGF 1），干扰IGF 1信号传导可概括疼痛恢复受损。在疼痛恢复的小鼠中，CD 11 c（+）小胶质细胞的耗竭或IGF 1信号传导的中断导致疼痛超敏反应的复发。我们的研究结果揭示了神经病理性疼痛缓解和复发的机制，为治疗策略提供了潜在的靶点。
Neuropathic pain is often caused by injury and diseases that affect the somatosensory system. Although pain development has been well studied, pain recovery mechanisms remain largely unknown. Here, we found that CD11c-expressing spinal microglia appear after the development of behavioral pain hypersensitivity following nerve injury. Nerve-injured mice with spinal CD11c(+) microglial depletion failed to recover spontaneously from this hypersensitivity. CD11c(+) microglia expressed insulin-like growth factor-1 (IGF1), and interference with IGF1 signaling recapitulated the impairment in pain recovery. In pain-recovered mice, the depletion of CD11c(+) microglia or the interruption of IGF1 signaling resulted in a relapse in pain hypersensitivity. Our findings reveal a mechanism for the remission and recurrence of neuropathic pain, providing potential targets for therapeutic strategies.