Nociceptive neurons detect cytokines in arthritis.
Nociceptive neurons detect cytokines in arthritis.
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DOI：
10.1186/s13075-014-0470-8
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发表时间：
2014
影响因子：
4.9
通讯作者：
Schaible HG
中科院分区：
文献类型：
--
作者：
Schaible HG
促炎细胞因子是类风湿性关节炎和骨关节炎等关节疾病发病机制的主要介质。本综述强调，肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6 和白细胞介素-17 等促炎细胞因子也是直接作用于伤害性系统的疼痛介质。部分伤害性感觉神经元表达这些细胞因子的受体，并且细胞因子的应用迅速改变这些神经元的兴奋性、离子电流和第二信使系统。通过诱导伤害性感觉神经元（C-纤维和一定比例的 Aδ-纤维）对关节中的机械刺激产生持续敏化（称为外周敏化的过程），这些细胞因子显着促进了关节许多疾病状态所特有的持续性痛觉过敏。此外，脊髓中与疾病相关的细胞因子的释放支持中枢敏化的产生。因此，促炎细胞因子的治疗性中和不仅可以减少炎症过程，而且可以通过逆转细胞因子的神经元效应来直接减轻痛觉过敏和疼痛。人们发现不同的细胞因子对神经元有不同的作用。肿瘤坏死因子-α 的中和可减少关节的机械和热痛觉过敏。白细胞介素 1β 的中和可减轻热痛觉过敏，而白细胞介素 6 和白细胞介素 17 的中和主要减轻机械痛觉过敏。这些不同的效应部分是通过影响感觉神经元中的不同靶分子来解释的。例如，在培养的感觉神经元中，肿瘤坏死因子-α 和白细胞介素-1β 上调参与热刺激转导的 TRPV1 离子通道，这与这些细胞因子在热痛觉过敏中的作用一致。相比之下，IL-17 上调 TRPV4 离子通道，该通道在机械刺激的转导中发挥作用。因此，中和细胞因子的镇痛潜力似乎取决于哪种细胞因子主要参与特定的疼痛状态。
Proinflammatory cytokines are major mediators in the pathogenesis of diseases of joints such as rheumatoid arthritis and osteoarthritis. This review emphasizes that proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1beta, interleukin-6 and interleukin-17 are also mediators of pain by directly acting on the nociceptive system. Proportions of nociceptive sensory neurons express receptors for these cytokines, and the application of cytokines rapidly changes the excitability, ion currents and second messenger systems of these neurons. By inducing persistent sensitization of nociceptive sensory neurons (C- and a proportion of Aδ-fibers) for mechanical stimuli in the joint (a process called peripheral sensitization), these cytokines significantly contribute to the persistent hyperalgesia typical for many disease states of the joint. In addition, the disease-associated release of cytokines in the spinal cord supports the generation of central sensitization. The therapeutic neutralization of proinflammatory cytokines thus not only reduces the process of inflammation but may directly reduce hyperalgesia and pain by reversing the neuronal effects of cytokines. It is emerging that different cytokines have different actions on neurons. The neutralization of tumor necrosis factor-alpha reduces both mechanical and thermal hyperalgesia of the joint. The neutralization of interleukin-1beta attenuates thermal hyperalgesia whereas the neutralization of interleukin-6 and interleukin-17 mainly reduces mechanical hyperalgesia. These different effects are partly explained by influencing different target molecules in sensory neurons. For example, in cultured sensory neurons tumor necrosis factor-alpha and interleukin-1beta upregulate the TRPV1 ion channel, which is involved in the transduction of heat stimuli, consistent with an effect of these cytokines in thermal hyperalgesia. By contrast, interleukin-17 upregulates the TRPV4 ion channel, which has a role in the transduction of mechanical stimuli. Thus, the analgesic potential of neutralizing cytokines seems to depend on which cytokine is mainly involved in the particular pain state.
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DOI：
10.1523/jneurosci.3795-08.2008
发表时间：
2008-12-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Binshtok AM;Wang H;Zimmermann K;Amaya F;Vardeh D;Shi L;Brenner GJ;Ji RR;Bean BP;Woolf CJ;Samad TA
通讯作者：
Samad TA
影响因子：
7.3
作者：
CUNHA, FQ;POOLE, S;FERREIRA, SH
通讯作者：
FERREIRA, SH
影响因子：
4.9
作者：
Boettger MK;Leuchtweis J;Kümmel D;Gajda M;Bräuer R;Schaible HG
通讯作者：
Schaible HG
影响因子：
7.4
作者：
Christianson CA;Corr M;Firestein GS;Mobargha A;Yaksh TL;Svensson CI
通讯作者：
Svensson CI
影响因子：
4
作者：
Kim, Cristina Fabiola;Moalem-Taylor, Gila
通讯作者：
Moalem-Taylor, Gila