TY - JOUR
T1 - Astrocytes contribute to pain gating in the spinal cord
AU - Xu, Qian
AU - Ford, Neil C.
AU - He, Shaoqiu
AU - Huang, Qian
AU - Anderson, Michael
AU - Chen, Zhiyong
AU - Yang, Fei
AU - Crawford, La Tasha K.
AU - Caterina, Michael J.
AU - Guan, Yun
AU - Dong, Xinzhong
N1 - Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved;
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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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U2 - 10.1126/sciadv.abi6287
DO - 10.1126/sciadv.abi6287
M3 - Article
C2 - 34730998
AN - SCOPUS:85118673369
SN - 2375-2548
VL - 7
JO - Science Advances
JF - Science Advances
IS - 45
M1 - eabi6287
ER -