Cellular Mechanisms of Neuroinflammatory Pain: The Role of Interleukin-1β

神經發炎性疼痛的細胞機轉︰探討Interleukin-1β的角色

宋俊松(Chun-Sung Sung) ； 汪志雄(Chih-Shung Wong)

《Acta Anaesthesiologica Taiwanica》 45卷2期 (2007/06) Pp. 103-109

摘要

脊髓背角對於疼痛訊息的傳遞與調控是重要的，interleukin-1β(IL-1β)不僅參與疼痛訊息的調控，也強化脊髓內痛覺神經元的wind-up作用。脊椎管注射IL-1β會先活化脊髓內p38 MAPK蛋白質，繼而活化並誘導脊髓內iNOS-NO cascade，並進而使大鼠表現過度痛覺反應；如果使用IL-1β受體拮抗劑(IL-1ra)、p38 MAPK抑制劑或是iNOS抑制劑預先做前驅性治療，可以有效抑制脊椎管注射IL-1β引起的上述的作用和反應，進而緩解發炎性疼痛在中樞神經系統內致敏化的程度。所以我們認為在脊椎管注射IL-1β的大鼠模式，對於演繹神經發炎性疼痛引起的中樞神經致敏化，是極具潛力的治療模式及思考方向。

關鍵字

Interleukin-1 ； Mitogen-activated protein kinases ； 一氧化氮合成 ； 一氧化氮 ； 痛覺過敏 ； 脊髓 ； 神經性發炎

並列摘要

Dorsal horn of the spinal cord is important in the transduction and modulation of various pain signals. Interleukin-1β(IL-1β) not only plays an important role in the nociceptive modulation but also enhances the spinal cord nociceptive neuron wind-up. Intrathecal (i.t.) administration of IL-1βactivates p38 mitogen-activated protein kinase (MAPK), and leads to induction of inducible nitric oxide synthase (iNOS) and release of nitric oxide (NO), which sensitizes the spinal nociceptors and produces thermal hyperalgesia and allodynia. I.t. pretreatment of IL-1β receptor antagonist (IL-1ra), p38 MAPK inhibitor or iNOS inhibitor, inhibits the i.t. IL-1β-induced NO levels and thermal hyperalgesia in rats, likely via either inhibiting the IL-1β-mediated p38MAPK activation and subsequent iNOS induction, or direct attenuation of the central iNOS activity, which therefore reduces the central sensitization of inflammatory pain. I.t. administration of IL-1β in rats provides an attractive model for studying the mechanisms and development of the treatment strategy of neuroinflammatory pain.

並列關鍵字

Interleukin-1 ； Mitogen-activated protein kinases ； Nitric oxide synthase ； Nitric oxide ； Hyperalgesia ； Spinal cord ； Neurogenic inflammation