神经病理性疼痛
促炎细胞因子
基因沉默
伤害
条件基因敲除
下调和上调
医学
痛觉超敏
神经科学
痛觉过敏
神经损伤
药理学
趋化因子
细胞生物学
表型
免疫学
化学
炎症
麻醉
生物
内科学
受体
基因
生物化学
作者
Lynda Zeboudj,George Sideris-Lampretsas,Rita Silva,Sabeha Al-Mudaris,Francesca Picco,Sarah Fox,David W. Chambers,Marzia Malcangio
摘要
Neuropathic pain remains poorly managed by current therapies, highlighting the need to improve our knowledge of chronic pain mechanisms. In neuropathic pain models, dorsal root ganglia (DRG) nociceptive neurons transfer miR-21 packaged in extracellular vesicles to macrophages that promote a proinflammatory phenotype and contribute to allodynia. Here we show that miR-21 conditional deletion in DRG neurons was coupled with lack of upregulation of chemokine CCL2 after nerve injury and reduced accumulation of CCR2-expressing macrophages, which showed TGF-β-related pathway activation and acquired an M2-like antinociceptive phenotype. Indeed, neuropathic allodynia was attenuated after conditional knockout of miR-21 and restored by TGF-βR inhibitor (SB431542) administration. Since TGF-βR2 and TGF-β1 are known miR-21 targets, we suggest that miR-21 transfer from injured neurons to macrophages maintains a proinflammatory phenotype via suppression of such an antiinflammatory pathway. These data support miR-21 inhibition as a possible approach to maintain polarization of DRG macrophages at an M2-like state and attenuate neuropathic pain.
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