INTERLEUKIN-33 MEDIATES FORMALIN-INDUCED INFLAMMATORY PAIN IN MICE

INTERLEUKIN-33 MEDIATES FORMALIN-INDUCED INFLAMMATORY PAIN IN MICE
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Interleukin-33 介导福尔马林诱导的小鼠炎症性疼痛

DOI:
10.1016/j.neuroscience.2013.03.019
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发表时间:
2013-06-25
期刊:
影响因子:
3.3
通讯作者:
Mi, W. -L.
Mi, W. -L.
中科院分区:
医学3区
文献类型:
--
作者:
Han, P.;Zhao, J.;Mi, W. -L.

文献摘要

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白细胞介素-33(IL-33)是IL-1家族的成员,自2003年被发现以来引起了越来越多的关注。IL-33与许多疾病有关,包括关节炎、哮喘、过敏以及心血管和传染病。然而,很少有研究探讨其在疼痛的传递和调制中的作用。本研究旨在探讨IL-33及其受体ST 2在福尔马林致炎性疼痛中的作用。我们发现皮下(s.c.,300 ng)和鞘内注射(i.t.,3 ng)的重组IL-33(rIL-33)不仅在正常小鼠中而且在福尔马林模型中增加了举爪和舔爪时间。阻断IL-33/ST 2信号传导的ST 2抗体的施用减轻了福尔马林诱导的自发性疼痛行为。此外,与野生型组相比,ST 2(-/-)小鼠表现出显着减少的疼痛行为,以及减少福尔马林诱导的超声发声。此外,ST 2抗体减轻了rIL-33对福尔马林小鼠疼痛行为的增强作用,表明IL-33通过其ST 2受体在疼痛调节中起作用。这些数据表明IL-33及其ST 2受体介导福尔马林诱导的炎性疼痛,因此这种细胞因子及其受体可能是开发镇痛药的新靶点。(c)2013年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Interleukin-33 (IL-33), a member of the IL-1 family, has attracted growing interest since its discovery in 2003. IL-33 has been implicated in many diseases, including arthritis, asthma, allergies, and cardiovascular and infectious diseases. However, few studies have investigated its role in the transmission and modulation of pain. The present study was designed to explore the possible roles of IL-33 and its receptor, ST2, in formalin-induced inflammatory pain in mice. We found that both subcutaneous (s.c., 300 ng) and intrathecal injection (i.t., 3 ng) of recombinant IL-33 (rIL-33) increased paw lifting and licking time not only in normal mice but also in formalin models. Administration of ST2 antibody, which blocked the IL-33/ST2 signaling, alleviated the formalin-induced spontaneous pain behavior. Moreover, the ST2(-/-) mice showed significantly decreased pain behavior, as well as reduced ultrasonic vocalization induced by formalin, compared with the wild-type group. Additionally, ST2 antibody alleviated the potentiating effects of rIL-33 on pain behavior in the formalin mice, indicating that IL-33 plays a role in pain modulation through its ST2 receptor. These data suggest IL-33 and its ST2 receptor mediate formalin-induced inflammatory pain, and as a result this cytokine and its receptor may be new targets for the development of analgesics. (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.