Impairment of interleukin-1 (IL-1) signaling reduces basal pain sensitivity in mice: Genetic, pharmacological and developmental aspects

Gilly Wolf, Raz Yirmiya*, Inbal Goshen, Kerstin Iverfeldt, Linda Holmlund, Kiyoshi Takeda, Yehuda Shavit

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


The cytokine interleukin-1 (IL-1) has been implicated in modulation of pain perception under various inflammatory conditions. The present study examined the hypothesis that IL-1 signaling is also involved in pain sensitivity under normal, non-inflammatory states, using three mouse models of impaired IL-1 signaling: targeted deletion of the IL-1 receptor type I or the IL-1 receptor accessory protein, and transgenic over-expression of IL-1 receptor antagonist within the brain and spinal cord. Thermal and mechanical pain sensitivity was assessed using the paw-flick, hot-plate, and von Frey tests. All mutant strains displayed significantly lower pain sensitivity, compared with their respective wild-type control strains, and with their parent strains (C57BL/6, CBA and 129), in all tests. In contrast, mice with targeted deletion of the p55 or p75 TNF receptor, or of interleukin-18, displayed normal or higher pain sensitivity compared to their respective controls. To differentiate between developmental vs. on-going effects of IL-1, mice were chronically treated with IL-1 receptor antagonist (IL-1ra) via osmotic micropumps, either in adulthood or prenatally (throughout the last 2 weeks of gestation). Adult mice that were treated with IL-1ra either in adulthood or in utero, displayed lower pain sensitivity, similar to mice with impaired IL-1 signaling. These findings suggest that basal pain sensitivity is genetically, developmentally and tonically influenced by IL-1 signaling.

Original languageAmerican English
Pages (from-to)471-480
Number of pages10
Issue number3
StatePublished - Aug 2003

Bibliographical note

Funding Information:
We would like to thank Professor Marshal Devor for his helpful suggestions. This project was partly supported by The Hebrew University of Jerusalem – Center for Research on Pain. R.Y. is a member of the Eric Roland Center for Neurodegenerative Diseases at the Hebrew University of Jerusalem. Facilitated by the Leon and Clara Sznajderman Chair of Psychology.


  • Cytokines
  • Interleukin-1
  • Interleukin-1 receptor antagonist
  • Mice
  • Pain sensitivity
  • Prenatal treatment


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