Interleukin-1 signaling is required for induction and maintenance of postoperative incisional pain: genetic and pharmacological studies in mice.
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 3h after the incision and lasting up to 48h 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 24h 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.
Wolf
Gilly
G
Department of Psychology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem 91905, Israel.
Livshits
Dina
D
Department of Psychology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem 91905, Israel.
Beilin
Benzion
B
Department of Anesthesiology, Rabin Medical Center, Hasharon Hospital, Petah Tiqwa 49372, Affiliated with Sackler School of Medicine, Tel Aviv University, Israel.
Yirmiya
Raz
R
Department of Psychology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem 91905, Israel.
Shavit
Yehuda
Y
Department of Psychology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem 91905, Israel. Electronic address: Udi.Shavit@huji.ac.il.
D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy / Q000503:physiopathology*; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1