β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain.
Abstract
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.
Type
Journal articlePermalink
https://hdl.handle.net/10161/13679Published Version (Please cite this version)
10.1038/ncomms12531Publication Info
Chen, Gang; Xie, Rou-Gang; Gao, Yong-Jing; Xu, Zhen-Zhong; Zhao, Lin-Xia; 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 https://hdl.handle.net/10161/13679.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Wei Chen
Associate Professor in Medicine
My general area of interest relates to how cancer develops and how to identify cancer
therapeutic agents. In particular I hope to identify molecular signals that underlie
the changes necessary for directing normal tissue to a malignant state in cancer.
Therefore, I have been studying how extracellular signals are deciphered by seven
trans-membrane receptors and their regulatory proteins to control cell proliferation
and differentiation. My major research focuses on studying GPCR, Smoothe
Ru-Rong Ji
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
Zhenzhong Xu
Adjunct Assistant Professor in the Department of Anesthesiology
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