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, Rou-Gang

dc.contributor.author

Gao, Yong-Jing

dc.contributor.author

Xu, Zhen-Zhong

dc.contributor.author

Zhao, Lin-Xia

dc.contributor.author

Bang, Sangsu

dc.contributor.author

Berta, Temugin

dc.contributor.author

Park, Chul-Kyu

dc.contributor.author

Lay, Mark

dc.contributor.author

Chen, Wei

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.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.identifier

https://www.ncbi.nlm.nih.gov/pubmed/27538456

dc.identifier

ncomms12531

dc.identifier.eissn

2041-1723

dc.identifier.uri

https://hdl.handle.net/10161/13679

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

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

duke.contributor.orcid

Ji, Ru-Rong|0000-0002-9355-3688

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

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Chen_ncomms_2016.pdf
Size:
2.12 MB
Format:
Adobe Portable Document Format