Astrocytes contribute to pain gating in the spinal cord.
Astrocytes contribute to pain gating in the spinal cord.
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星形胶质细胞有助于脊髓疼痛门控。
DOI：
10.1126/sciadv.abi6287
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发表时间：
2021-11-05
期刊：
影响因子：
13.6
通讯作者：
Dong X
中科院分区：
文献类型：
--
作者：
Xu Q;Ford NC;He S;Huang Q;Anderson M;Chen Z;Yang F;Crawford LK;Caterina MJ;Guan Y;Dong X
脊髓星形胶质细胞是疼痛门控的重要组成部分，并发挥非神经元的疼痛控制。基于疼痛的门控理论，已经开发了各种疼痛疗法，该理论假设由大直径传入纤维（Aβ-纤维）介导的非疼痛感觉输入可以减弱传递到大脑的有害信号。到目前为止，这一理论只关注神经元机制。在这里，我们确定了一个前所未有的功能，星形胶质细胞在门控的伤害性信号传递的神经激肽1受体阳性（NK 1 R+）的投射神经元在脊髓。电刺激未处理小鼠外周Aβ纤维可激活脊髓星形胶质细胞，进而通过激活内源性腺苷能机制诱导NK 1 R+神经元的长期抑制（LTD）和抗伤害感受。通过药理学、化学遗传学和光遗传学操作抑制星形胶质细胞活化，阻断了NK 1 R+神经元中LTD的诱导和Aβ纤维刺激的疼痛抑制。总的来说，我们的研究通过激活Aβ纤维引入星形胶质细胞作为疼痛门控的重要组成部分，从而对疼痛进行非神经元控制。
Spinal cord astrocytes represent an important component of pain gating and exert nonneuronal control of pain. Various pain therapies have been developed on the basis of the gate control theory of pain, which postulates that nonpainful sensory inputs mediated by large-diameter afferent fibers (Aβ-fibers) can attenuate noxious signals relayed to the brain. To date, this theory has focused only on neuronal mechanisms. Here, we identified an unprecedented function of astrocytes in the gating of nociceptive signals transmitted by neurokinin 1 receptor–positive (NK1R+) projection neurons in the spinal cord. Electrical stimulation of peripheral Aβ-fibers in naïve mice activated spinal astrocytes, which in turn induced long-term depression (LTD) in NK1R+ neurons and antinociception through activation of endogenous adenosinergic mechanisms. Suppression of astrocyte activation by pharmacologic, chemogenetic, and optogenetic manipulations blocked the induction of LTD in NK1R+ neurons and pain inhibition by Aβ-fiber stimulation. Collectively, our study introduces astrocytes as an important component of pain gating by activation of Aβ-fibers, which thus exert nonneuronal control of pain.
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