Interleukin-1αβ gene-deficient mice show reduced nociceptive sensitivity in models of inflammatory and neuropathic pain but not post-operative pain

Prisca Honore, Carrie L. Wade, Chengmin Zhong, Richard R. Harris, C. Wu, Tariq Ghayur, Yoichiro Iwakura, Michael W. Decker, Connie Faltynek, James Sullivan, Michael F. Jarvis

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

The pro-inflammatory cytokine interleukin-1 (IL-1) has been implicated in both inflammatory processes and nociceptive neurotransmission. To further investigate the role of IL-1 in different pain states, gene-disrupted mice lacking both IL-1α and IL-1β genes (IL-1αβ (-/-)) were characterized in inflammatory, neuropathic, and post-operative pain models. IL-1αβ (-/-) mice showed normal sensorimotor function as measured by the rotorod assay compared to control mice (BALB/c). Acute and persistent formalin-induced nocifensive behaviors were reduced by 20% in IL-1αβ (-/-) mice as compared to control mice. IL-1αβ (-/-) mice also showed reduced inflammatory thermal and mechanical hyperalgesia compared to controls following the intraplantar administration of carrageenan or complete Freund's adjuvant (CFA). The duration of inflammatory hyperalgesia was shortened in IL-1αβ (-/-) mice versus controls in the CFA model. In contrast, deletion of IL-1αβ did not change the extent or the duration of post-operative pain developing after skin incision of the hind paw. Finally, time to onset, duration, and magnitude of mechanical allodynia were reduced in two models of neuropathic pain, spinal nerve L5-L6 ligation and chronic constriction injury of the sciatic nerve, in IL-1αβ (-/-) mice versus controls. These results demonstrate that IL-1αβ modulates both the generation and the maintenance of inflammatory and chronic neuropathic pain and that IL-1 may modulate nociceptive sensitivity to a greater extent in conditions of chronic as compared to acute pain.

Original languageEnglish (US)
Pages (from-to)355-364
Number of pages10
JournalBehavioural Brain Research
Volume167
Issue number2
DOIs
StatePublished - Feb 28 2006

Keywords

  • Chronic pain
  • Cytokines
  • Mirror-image pain

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