Cytokine involvement in dynorphin-induced allodynia

Tinna M. Laughlin, John R. Bethea, Robert P. Yezierski, George L. Wilcox

Research output: Contribution to journalArticle

138 Scopus citations

Abstract

Dynorphin A is an endogenous opioid peptide, which has previously been shown to produce a long-lasting allodynia and hyperalgesia in mice, behavioral states consistent with signs of clinically observed neuropathic pain. This dynorphin-induced allodynia was used as a pharmacological, central model of neuropathic pain. In this study, we examined the involvement of the cytokine IL-1β, the transcription factor nuclear factor kappa B (NF-κB), and de novo protein synthesis in the development of allodynia induced by intrathecal (i.t.) administration of dynorphin in male ICR mice. Pretreatment with the protein synthesis inhibitor cycloheximide (0.3-85nmol), the NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC) (0.001-1000pmol), the IL-1 receptor antagonist (IL-1ra) protein (0.01-100ng), the caspase-1 inhibitor (YVAD) (0.1-300pmol), and the anti-inflammatory cytokine IL-10 (0.1-300ng) all dose-dependently reduced the induction of dynorphin-induced allodynia. Finally, IL-10 administered within the first 24h after the dynorphin insult prevented the development of chronic allodynia. These results demonstrate that the anti-inflammatory cytokines IL-10 and IL-1ra impede the development of dynorphin-induced allodynia. These results also suggest that production of new proteins through NF-κB activation is required for the induction of allodynia. We speculate that IL-1ra, IL-10, PDTC and cycloheximide interfere with the central pro-inflammatory cascade. Modulation of cytokine activity in the spinal cord may therefore prove to be an effective therapeutic strategy for the treatment of chronic pain. Copyright (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)159-167
Number of pages9
JournalPain
Volume84
Issue number2-3
DOIs
StatePublished - Feb 1 2000

Keywords

  • Cytokines
  • IL-10
  • Interleukin-1beta
  • Neuropathic pain
  • NF-κB
  • Protein synthesis

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Neuroscience(all)
  • Pharmacology
  • Clinical Psychology

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  • Cite this

    Laughlin, T. M., Bethea, J. R., Yezierski, R. P., & Wilcox, G. L. (2000). Cytokine involvement in dynorphin-induced allodynia. Pain, 84(2-3), 159-167. https://doi.org/10.1016/S0304-3959(99)00195-5