Interleukin-1 signaling is required for induction and maintenance of postoperative incisional pain: Genetic and pharmacological studies in mice

Gilly Wolf, Dina Livshits, Benzion Beilin, Raz Yirmiya, Yehuda Shavit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Postoperative incisional pain is characterized by persistent acute pain in the area of the cut, and is associated with release of proinflammatory cytokines, including interleukin-1 (IL-1), which play important hyperalgesic and allodynic roles in various inflammatory conditions. In the present study, we tested the role of IL-1 signaling in postoperative incisional pain using three mouse strains impaired in IL-1 signaling due to deletion of the IL-1 type I receptor on a mixed genetic background (IL-1rKO) or congenic background (IL-1rKOCog), or due to transgenic over-expression of IL-1 receptor antagonist (IL-1raTG). We used the relevant wild-type (WT) mice both as controls for the mutant strains, and for assessing the effects of pharmacological blockade of IL-1-signaling. Mechanosensitivity was assessed using the von-Frey filament test before, and up to 4 days following plantar incision, an animal model of postoperative pain. WT mice developed significant allodynia in the incised, compared with the intact, hind-paw beginning 3 h after the incision and lasting up to 48 h postoperatively. In contrast, IL-1rKO, IL-1rKOCog, and IL-1raTG mice, as well as WT mice chronically treated with IL-1ra, did not display increased mechanical pain sensitivity in either hind-paw. To test the hypothesis that IL-1-signaling is also involved in the maintenance of postoperative pain, WT mice were acutely treated with IL-1ra 24 h following the incision, when allodynia was already evident. This treatment reversed the allodynic response throughout the observation period. Together, these findings suggest that IL-1 plays a critical role in the development and maintenance of postoperative incisional pain.

Original languageAmerican English
Pages (from-to)1072-1077
Number of pages6
JournalBrain, Behavior, and Immunity
Volume22
Issue number7
DOIs
StatePublished - Oct 2008

Bibliographical note

Funding Information:
This work was partly supported by a grant from the Israel Science Foundation – The Charles H. Revson Foundation (Grant No. 799/03) (R.Y. and Y.S.), and by a grant from the Israel Foundations Trustees (G.W.). This work was facilitated by the Leon and Clara Sznajderman Chair of Psychology (Y.S.). We thank Prof. K. Iverfeldt for the IL-1raTG mice, and Amgen Inc., Thousand Oaks, CA, for the generous gift of L-1ra. R.Y. and Y.S. are members of the Hebrew University Center for Research on Pain and of the Eric Roland Center for Neurodegenerative Diseases at the Hebrew University of Jerusalem

Keywords

  • Allodynia
  • Interleukin-1 (IL-1)
  • Interleukin-1 receptor antagonist (IL-1ra)
  • Plantar incision
  • Postoperative pain
  • Proinflammatory cytokines

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