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β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain.

dc.contributor.author Chen, Gang
dc.contributor.author Xie, R-G
dc.contributor.author Gao, Y-J
dc.contributor.author Xu, Zhenzhong
dc.contributor.author Zhao, L-X
dc.contributor.author Bang, Sangsu
dc.contributor.author Berta, T
dc.contributor.author Park, C-K
dc.contributor.author Lay, M
dc.contributor.author Chen, W
dc.contributor.author Ji, Ru-Rong
dc.coverage.spatial England
dc.date.accessioned 2017-02-24T19:28:07Z
dc.date.available 2017-02-24T19:28:07Z
dc.date.issued 2016-08-19
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/27538456
dc.identifier ncomms12531
dc.identifier.uri http://hdl.handle.net/10161/13679
dc.description.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.
dc.language eng
dc.relation.ispartof Nat Commun
dc.relation.isversionof 10.1038/ncomms12531
dc.title β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/27538456
pubs.begin-page 12531
pubs.organisational-group Anesthesiology
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Neurobiology
pubs.organisational-group School of Medicine
pubs.publication-status Published online
pubs.volume 7
dc.identifier.eissn 2041-1723


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