Interleukin-1alphabeta gene-deficient mice show reduced nociceptive sensitivity in models of inflammatory and neuropathic pain but not post-operative pain.
Interleukin-1alphabeta gene-deficient mice show reduced nociceptive sensitivity in models of inflammatory and neuropathic pain but not post-operative pain.
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发表时间：
2006
影响因子：
2.7
通讯作者：
P. Honore;C. Wade;C. Zhong;R. Harris;C. Wu;T. Ghayur;Y. Iwakura;M. Decker;C. Faltynek;J. Sullivan;M. Jarvis
中科院分区：
文献类型：
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作者：
P. Honore;C. Wade;C. Zhong;R. Harris;C. Wu;T. Ghayur;Y. Iwakura;M. Decker;C. Faltynek;J. Sullivan;M. Jarvis
促炎细胞因子白细胞介素-1 (IL-1) 与炎症过程和伤害性神经传递有关。为了进一步研究 IL-1 在不同疼痛状态中的作用，在炎症、神经性和术后疼痛模型中对缺乏 IL-1α 和 IL-1β 基因 (IL-1αβ (-/-)) 的基因破坏小鼠进行了表征。与对照小鼠 (BALB/c) 相比，通过旋转杆测定测量，IL-1alphabeta (-/-) 小鼠表现出正常的感觉运动功能。与对照小鼠相比，IL-1alphabeta (-/-) 小鼠的急性和持续性福尔马林诱导的伤害行为减少了 20%。在足底内施用角叉菜胶或完全弗氏佐剂 (CFA) 后，与对照组相比，IL-1alphabeta (-/-) 小鼠还表现出炎性热和机械痛觉过敏减少。在 CFA 模型中，与对照组相比，IL-1alphabeta (-/-) 小鼠的炎症性痛觉过敏持续时间缩短。相比之下，IL-1αβ的缺失并没有改变后爪皮肤切口后发生的术后疼痛的程度或持续时间。最后，与对照组相比，IL-1alphabeta (-/-) 小鼠的两种神经性疼痛（脊神经 L5-L6 结扎和坐骨神经慢性压迫损伤）模型中机械性异常性疼痛的发作时间、持续时间和强度均有所减少。这些结果证明IL-1αβ调节炎性疼痛和慢性神经性疼痛的产生和维持，并且与急性疼痛相比，IL-1可以在慢性病症中更大程度地调节伤害性敏感性。
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.