神经病理性疼痛
伤害感受器
PI3K/AKT/mTOR通路
背根神经节
伤害
医学
小胶质细胞
神经科学
化学
信号转导
细胞生物学
受体
脊髓
麻醉
内科学
生物
炎症
作者
Chen L,Yeting Hu,Si-Liang Wang,Kelei Cao,Weihao Mai,Sha W,Huan M,Yu Gao,Shumin Duan,Yungui Wang,Zaifeng Gao
标识
DOI:10.1101/2021.10.29.466458
摘要
Abstract Neuropathic pain is a refractory condition that involves de novo protein synthesis in the nociceptive pathway. The mechanistic target of rapamycin (mTOR) is a master regulator of protein translation; however, mechanisms underlying its role in neuropathic pain remain elusive. Using spared nerve injury-induced neuropathic pain model, we found that mTOR is preferentially activated in large-diameter dorsal root ganglion (DRG) neurons and spinal microglia. However, selective ablation of mTOR in DRG neurons, rather than microglia, alleviated neuropathic pain. We show that injury- induced mTOR activation promoted transcriptional induction of NPY likely via signal transducer and activator of transcription 3 (STAT3) phosphorylation. NPY further acted primarily on Y2 receptors (Y2R) to enhance nociceptor excitability. Peripheral replenishment of NPY reversed pain alleviation upon mTOR removal, whereas Y2R antagonists prevented pain restoration. Our findings reveal an unexpected link between mTOR and NPY in promoting nociceptor sensitization and neuropathic pain, through NPY/Y2R signaling-mediated intra-ganglionic transmission.
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