beta-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain
- Authors
- Chen, Gang; Xie, Rou-Gang; Gao, Yong-Jing; Xu, Zhen-Zhong; Zhao, Lin-Xia; Bang, Sangsu; Berta, Temugin; Park, Chul-Kyu; Lay, Mark; Chen, Wei; Ji, Ru-Rong
- Issue Date
- Aug-2016
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE COMMUNICATIONS, v.7
- Journal Title
- NATURE COMMUNICATIONS
- Volume
- 7
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/8071
- DOI
- 10.1038/ncomms12531
- ISSN
- 2041-1723
- Abstract
- Mechanisms of acute pain transition to chronic pain are not fully understood. Here we demonstrate an active role of beta-arrestin 2 (Arrb2) in regulating spinal cord NMDA receptor (NMDAR) function and the duration of pain. Intrathecal injection of the mu-opioid receptor agonist [D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin produces paradoxical behavioural responses: early-phase analgesia and late-phase mechanical allodynia which requires NMDAR; both phases are prolonged in Arrb2 knockout (KO) mice. Spinal administration of NMDA induces GluN2B-dependent mechanical allodynia, which is prolonged in Arrb2-KO mice and conditional KO mice lacking Arrb2 in presynaptic terminals expressing Nav1.8. Loss of Arrb2 also results in prolongation of inflammatory pain and neuropathic pain and enhancement of GluN2B-mediated NMDA currents in spinal lamina IIo not lamina I neurons. Finally, spinal over-expression of Arrb2 reverses chronic neuropathic pain after nerve injury. Thus, spinal Arrb2 may serve as an intracellular gate for acute to chronic pain transition via desensitization of NMDAR.
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