Interleukin-1 signaling modulates stress-induced analgesia.
Exposure to stressful stimuli is often accompanied by reduced pain sensitivity, termed "stress-induced analgesia" (SIA). In the present study, the hypothesis that interleukin-1 (IL-1) may play a modulatory role in SIA was examined. Two genetic mouse models impaired in IL-1-signaling and their wild-type (WT) controls were employed. Another group of C57 mice was acutely administered with IL-1 receptor antagonist (IL-1ra). Mice were exposed to 2min swim stress at one of three water temperatures: 32 degrees C (mild stress), 20-23 degrees C (moderate stress), or 15 degrees C (severe stress); and then tested for pain sensitivity using the hot-plate test. Corticosterone levels were assessed in separate groups of WT and mutant mice following exposure to the three types of stress. Mild stress induced significant analgesia in the two WT strains and saline-treated mice, but not in the mutant strains or the IL-1ra-treated mice. Similarly, mild stress induced significantly elevated corticosterone levels in WT mice, and blunted corticosterone response in mutant mice. In contrast, both WT and mutant strains, as well as IL-1ra-treated mice, displayed analgesic and corticosterone responses following moderate and severe stress. Interestingly, the analgesic response to moderate stress was markedly potentiated in the mutant strains, as compared with their WT controls. The present results support our previous findings that in the absence of IL-1, stress response to mild stress is noticeably diminished. However, the analgesic response to moderate stress is markedly potentiated in mice with impaired IL-1 signaling, corroborating the anti-analgesic role of IL-1 in several pain modulatory conditions, including SIA.
Wolf
G
G
Department of Psychology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem 91905, Israel.
Yirmiya
R
R
Kreisel
T
T
Goshen
I
I
Weidenfeld
J
J
Poole
S
S
Shavit
Y
Y
D000698:Analgesia / Q000523:psychology; D000818:Animals; D003345:Corticosterone / Q000097:blood; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010146:Pain / Q000378:metabolism*; D017288:Pain Threshold / Q000502:physiology*; D053573:Receptors, Interleukin-1 Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism*
D007375:Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D003345:Corticosterone