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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chen, G; Xie, R-G; Gao, Y-J; Xu, Z-Z; Zhao, L-X; Bang, S; Berta, T; Park, C-K; Lay, M; Chen, W; Ji, R-R

Published Date

  • August 19, 2016

Published In

Volume / Issue

  • 7 /

Start / End Page

  • 12531 -

PubMed ID

  • 27538456

Pubmed Central ID

  • 27538456

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms12531

Language

  • eng

Conference Location

  • England