Nociceptors are interleukin-1beta sensors.
Nociceptors are interleukin-1beta sensors.
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DOI：
10.1523/jneurosci.3795-08.2008
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发表时间：
2008-12-24
期刊：
影响因子：
--
通讯作者：
Samad TA
中科院分区：
文献类型：
--
作者：
Binshtok AM;Wang H;Zimmermann K;Amaya F;Vardeh D;Shi L;Brenner GJ;Ji RR;Bean BP;Woolf CJ;Samad TA
炎症的一个基本特征是炎症组织部位的疼痛敏感度升高。这是由于免疫和损伤细胞局部释放伤害性感受器敏感剂，包括前列腺素E2、缓激肽和神经生长因子，这些敏感剂降低了痛觉感受器的阈值，增加了外周终末的兴奋性，使它们现在对无害的刺激--外周敏化现象--做出反应。在这里，我们展示了致炎细胞因子IL-1β(IL-1β)除了产生炎症和诱导几种伤害性感受器敏化物质的合成外，还快速和直接地激活伤害性感受器产生动作电位和诱导疼痛超敏。IL-1β以p38丝裂原活化蛋白激酶(P38 MAP)依赖的方式发挥作用，通过解除河豚毒素抗性电压门控钠通道的静息缓慢失活来增加伤害性感受器的兴奋性，并在阈值附近增强持续的河豚毒素抗性电流。通过充当IL-1β传感器，伤害性感受器可以直接发出正在进行的组织炎症存在的信号。
A cardinal feature of inflammation is heightened pain sensitivity at the site of the inflamed tissue. This results from the local release by immune and injured cells of nociceptor sensitizers, including prostaglandin E2, bradykinin, and nerve growth factor, that reduce the threshold and increase the excitability of the peripheral terminals of nociceptors so that they now respond to innocuous stimuli: the phenomenon of peripheral sensitization. We show here that the proinflammatory cytokine interleukin-1β (IL-1β), in addition to producing inflammation and inducing synthesis of several nociceptor sensitizers, also rapidly and directly activates nociceptors to generate action potentials and induce pain hypersensitivity. IL-1β acts in a p38 mitogen-activated protein kinase (p38 MAP kinase)-dependent manner, to increase the excitability of nociceptors by relieving resting slow inactivation of tetrodotoxin-resistant voltage-gated sodium channels and also enhances persistent TTX-resistant current near threshold. By acting as an IL-1β sensor, nociceptors can directly signal the presence of ongoing tissue inflammation.