title: Impairment of interleukin-1 (IL-1) signaling reduces basal pain sensitivity in mice: genetic, pharmacological and developmental aspects.
abstract: 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.
authors.affiliation: Department of Psychology, The Hebrew University, Mount Scopus, Jerusalem 91905, Israel Department of Neurochemistry and Neurotoxicology, Stockholm University, Stockholm, Sweden Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
authors.forename: Gilly
authors.initials: G
authors.lastname: Wolf
authors.forename: Raz
authors.initials: R
authors.lastname: Yirmiya
authors.forename: Inbal
authors.initials: I
authors.lastname: Goshen
authors.forename: Kerstin
authors.initials: K
authors.lastname: Iverfeldt
authors.forename: Linda
authors.initials: L
authors.lastname: Holmlund
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shavit
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010146:Pain / Q000235:genetics* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000008:administration & dosage; D015398:Signal Transduction / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha