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

Publication ,  Journal Article
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 in: Nat Commun
August 19, 2016

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 19, 2016

Volume

7

Start / End Page

12531

Location

England

Related Subject Headings

  • beta-Arrestin 2
  • Time Factors
  • Substantia Gelatinosa
  • Spinal Cord Dorsal Horn
  • Receptors, Opioid, mu
  • Receptors, N-Methyl-D-Aspartate
  • Peripheral Nerve Injuries
  • Neurons
  • Neuralgia
  • N-Methylaspartate
 

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Chen, G., Xie, R.-G., Gao, Y.-J., Xu, Z.-Z., Zhao, L.-X., Bang, S., … Ji, R.-R. (2016). β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain. Nat Commun, 7, 12531. https://doi.org/10.1038/ncomms12531
Chen, Gang, Rou-Gang Xie, Yong-Jing Gao, Zhen-Zhong Xu, Lin-Xia Zhao, Sangsu Bang, Temugin Berta, et al. “β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain.Nat Commun 7 (August 19, 2016): 12531. https://doi.org/10.1038/ncomms12531.
Chen G, Xie R-G, Gao Y-J, Xu Z-Z, Zhao L-X, Bang S, et al. β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain. Nat Commun. 2016 Aug 19;7:12531.
Chen, Gang, et al. “β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain.Nat Commun, vol. 7, Aug. 2016, p. 12531. Pubmed, doi:10.1038/ncomms12531.
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. β-arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain. Nat Commun. 2016 Aug 19;7:12531.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 19, 2016

Volume

7

Start / End Page

12531

Location

England

Related Subject Headings

  • beta-Arrestin 2
  • Time Factors
  • Substantia Gelatinosa
  • Spinal Cord Dorsal Horn
  • Receptors, Opioid, mu
  • Receptors, N-Methyl-D-Aspartate
  • Peripheral Nerve Injuries
  • Neurons
  • Neuralgia
  • N-Methylaspartate