A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation: Respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance

Zhi Ye Zhuang, Yeong Ray Wen, De Ren Zhang, Tiziana Borsello, Christophe Bonny, Gary R. Strichartz, Isabelle Decosterd, Ru Rong Ji

Research output: Contribution to journalArticlepeer-review

Abstract

Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain produced by spinal nerve ligation (SNL) (L5). SNL induced a slow (>3 d) and persistent (>21 d) activation of JNK, in particular JNK1, in GFAP-expressing astrocytes in the spinal cord. In contrast, p38 mitogen-activated protein kinase activation was found in spinal microglia after SNL, which had fallen to near basal level by 21 d. Intrathecal infusion of a JNK peptide inhibitor, D-JNKI-1, did not affect normal pain responses but potently prevented and reversed SNL-induced mechanical allodynia, a major symptom of neuropathic pain. Intrathecal D-JNKI-1 also suppressed SNL-induced phosphorylation of the JNK substrate, c-Jun, in spinal astrocytes. However, SNL-induced upregulation of GFAP was not attenuated by spinal D-JNKI-1 infusion. Furthermore, SNL induced a rapid (

Original languageEnglish
Pages (from-to)3551-3560
Number of pages10
JournalJournal of Neuroscience
Volume26
Issue number13
DOIs
Publication statusPublished - Mar 29 2006

Keywords

  • Dorsal root ganglion
  • Glia
  • MAP kinase
  • Nerve injury
  • Neuropathy
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation: Respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance'. Together they form a unique fingerprint.

Cite this