β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain.
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Mechanisms of acute pain transition to chronic pain are not fully understood. Here we demonstrate an active role of β-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.
Published Version (Please cite this version)10.1038/ncomms12531
Publication InfoChen, Gang; Xie, R-G; Gao, Y-J; Xu, Zhenzhong; Zhao, L-X; Bang, Sangsu; ... Ji, Ru-Rong (2016). β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain. Nat Commun, 7. pp. 12531. 10.1038/ncomms12531. Retrieved from http://hdl.handle.net/10161/13679.
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Assistant Professor in Anesthesiology
Distinguished Professor of Anesthesiology, in the School of Medicine
Chronic pain is a major health problem in the US, affecting 100 million Americans. The long-term goal of the lab is to identify molecular and cellular mechanisms that underlie the genesis of chronic pain and, furthermore, to develop novel pain therapeutics that can target these mechanisms. We are interested in the following questions. (1) How do neuroinflammation and activation of glial cells (microglia and astrocytes) regulate pain and spinal cord synaptic plasticity via neuro-glia
Adjunct Assistant Professor in the Department of Anesthesiology
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