Interleukin-1alphabeta gene-deficient mice show reduced nociceptive sensitivity in models of inflammatory and neuropathic pain but not post-operative pain.
The pro-inflammatory cytokine interleukin-1 (IL-1) has been implicated in both inflammatory processes and nociceptive neurotransmission. To further investigate the role of IL-1 in different pain states, gene-disrupted mice lacking both IL-1alpha and IL-1beta genes (IL-1alphabeta (-/-)) were characterized in inflammatory, neuropathic, and post-operative pain models. IL-1alphabeta (-/-) mice showed normal sensorimotor function as measured by the rotorod assay compared to control mice (BALB/c). Acute and persistent formalin-induced nocifensive behaviors were reduced by 20% in IL-1alphabeta (-/-) mice as compared to control mice. IL-1alphabeta (-/-) mice also showed reduced inflammatory thermal and mechanical hyperalgesia compared to controls following the intraplantar administration of carrageenan or complete Freund's adjuvant (CFA). The duration of inflammatory hyperalgesia was shortened in IL-1alphabeta (-/-) mice versus controls in the CFA model. In contrast, deletion of IL-1alphabeta did not change the extent or the duration of post-operative pain developing after skin incision of the hind paw. Finally, time to onset, duration, and magnitude of mechanical allodynia were reduced in two models of neuropathic pain, spinal nerve L5-L6 ligation and chronic constriction injury of the sciatic nerve, in IL-1alphabeta (-/-) mice versus controls. These results demonstrate that IL-1alphabeta modulates both the generation and the maintenance of inflammatory and chronic neuropathic pain and that IL-1 may modulate nociceptive sensitivity to a greater extent in conditions of chronic as compared to acute pain.
Honore
Prisca
P
Abbott laboratories, Dept R4N5, Bldg AP9A-LL, 100 Abbott Park Road, Abbott Park, IL 60064, USA. marie.honore@abbott.com
Wade
Carrie L
CL
Zhong
Chengmin
C
Harris
Richard R
RR
Wu
C
C
Ghayur
Tariq
T
Iwakura
Yoichiro
Y
Decker
Michael W
MW
Faltynek
Connie
C
Sullivan
James
J
Jarvis
Michael F
MF
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000235:genetics / Q000503:physiopathology*; D007249:Inflammation / Q000150:complications / Q000503:physiopathology*; D007375:Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D017288:Pain Threshold / Q000502:physiology*; D010149:Postoperative Pain / Q000503:physiopathology; D011897:Random Allocation; D045442:Rotarod Performance Test; D020426:Sciatic Neuropathy / Q000150:complications / Q000503:physiopathology*
D007375:Interleukin-1