VPS26A-SNX27 interaction-dependent MGLUR5 recycling in dorsal horn neurons mediates neuropathic pain in rats

Tzer Bin Lin, Cheng Yuan Lai, Ming Chun Hsieh, Hsueh Hsiao Wang, Jen Kun Cheng, Yat Pang Chau, Gin Den Chen, Hsien Yu Peng

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Retromer, which crucially contributes to endosomal sorting machinery through the retrieval and recycling of signaling receptors away from degradation, has been identified as a critical element for glutamatergic-receptor-dependent neural plasticity at excitatory synapses. We observed it accompanied by behavioral allodynia; neuropathic injury time-dependently enhanced VPS26A and SNX27 expression; VPS26A-SNX27 coprecipitation; and VPS26A-positive, SNX27-positive, and VPS26A-SNX27 double-labeled immunoreactivity in the dorsal horn of Sprague Dawley rats that were all sufficiently ameliorated through the focal knock-down of spinal VPS26A expression. Although the knock-down of spinal SNX27 expression exhibited similar effects, spinal nerve ligation (SNL)-enhanced VPS26A expression remained unaffected. Moreover, SNL also increased membrane-bound and total mGluR5 abundance, VPS26A-bound SNX27 and mGluR5 and mGluR5-bound VPS26A and SNX27 coprecipitation, and mGluR5-positive and VPS26A/SNX27/mGluR5 triple-labeled immunoreactivity in the dorsal horn, and these effects were all attenuated through the focal knock-down of spinal VPS26A and SNX27 expression. Although administration with MPEP adequately ameliorated SNL-associated allodynia, mGluR5 expression, and membrane insertion, SNL-enhanced VPS26A and SNX27 expression were unaffected. Together, these results suggested a role of spinal VPS26A-SNX27-dependentmGluR5recycling in the development of neuropathic pain. This is the first study that links retromer-associated sorting machinery with the spinal plasticity underlying pain hypersensitivity and proposes the possible pathophysiological relevance of endocytic recycling in pain pathophysiology through the modification of glutamatergic mGluR5 recycling.

Original languageEnglish
Pages (from-to)14943-14955
Number of pages13
JournalJournal of Neuroscience
Volume35
Issue number44
DOIs
Publication statusPublished - Nov 4 2015

Fingerprint

Posterior Horn Cells
Spinal Nerves
Neuralgia
Ligation
Hyperalgesia
Pain
Neuronal Plasticity
Membranes
Recycling
Synapses
Sprague Dawley Rats
Hypersensitivity
Wounds and Injuries
Spinal Cord Dorsal Horn

Keywords

  • Allodynia
  • MGluR5
  • Neuropathic pain
  • Retromer
  • SNX27
  • VPS26

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

VPS26A-SNX27 interaction-dependent MGLUR5 recycling in dorsal horn neurons mediates neuropathic pain in rats. / Lin, Tzer Bin; Lai, Cheng Yuan; Hsieh, Ming Chun; Wang, Hsueh Hsiao; Cheng, Jen Kun; Chau, Yat Pang; Chen, Gin Den; Peng, Hsien Yu.

In: Journal of Neuroscience, Vol. 35, No. 44, 04.11.2015, p. 14943-14955.

Research output: Contribution to journalArticle

Lin, Tzer Bin ; Lai, Cheng Yuan ; Hsieh, Ming Chun ; Wang, Hsueh Hsiao ; Cheng, Jen Kun ; Chau, Yat Pang ; Chen, Gin Den ; Peng, Hsien Yu. / VPS26A-SNX27 interaction-dependent MGLUR5 recycling in dorsal horn neurons mediates neuropathic pain in rats. In: Journal of Neuroscience. 2015 ; Vol. 35, No. 44. pp. 14943-14955.
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AU - Peng, Hsien Yu

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