CXCL5 mediates UVB irradiation-induced pain.
CXCL5 mediates UVB irradiation-induced pain.
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DOI：
10.1126/scitranslmed.3002193
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发表时间：
2011-07-06
影响因子：
17.1
通讯作者：
McMahon SB
中科院分区：
文献类型：
--
作者：
Dawes JM;Calvo M;Perkins JR;Paterson KJ;Kiesewetter H;Hobbs C;Kaan TK;Orengo C;Bennett DL;McMahon SB
由于现有疗法的局限性，许多持续性疼痛状态（持续数小时、数天或更长时间的疼痛）治疗效果不佳。镇痛药，如非甾体抗炎药和阿片类药物，往往提供不完全的疼痛缓解和长期使用的结果在严重的副作用的发展。识别各种类型疼痛的关键介质可以改善这种疗法。在这里，我们测试的假设，迄今尚未认识到的细胞因子和趋化因子可能作为介质的炎症疼痛。我们使用紫外线B（UVB）照射诱导人类和大鼠对疼痛的持续、异常敏感性。超过90种不同的炎症介质的表达进行了测量，在治疗的皮肤在UVB诱导的超敏反应与定制的聚合酶链反应阵列的高峰。两个物种之间的总体表达谱存在显著正相关。先前显示与疼痛超敏反应相关的几种基因[白细胞介素-1 β（IL-1β）、IL-6和环氧合酶-2（考克斯-2）]的表达在UVB暴露后显著增加，并且几种趋化因子（CCL 2、CCL 3、CCL 4、CCL 7、CCL 11、CXCL 1、CXCL 2、CXCL 4、CXCL 7和CXCL 8）出现失调。在测量的基因中，CXCL 5在人体皮肤中被UVB处理诱导到最大程度;当注射到大鼠皮肤中时，CXCL 5再现了UVB照射引起的机械超敏反应。这种超敏反应与中性粒细胞和巨噬细胞浸润到真皮中有关，中和CXCL 5的作用减弱了异常的疼痛样行为。我们的研究结果表明，趋化因子CXCL 5是UVB诱导的炎症性疼痛的外周介质，可能在人类以及大鼠。
Many persistent pain states (pain lasting for hours, days, or longer) are poorly treated because of the limitations of existing therapies. Analgesics such as nonsteroidal anti-inflammatory drugs and opioids often provide incomplete pain relief and prolonged use results in the development of severe side effects. Identification of the key mediators of various types of pain could improve such therapies. Here, we tested the hypothesis that hitherto unrecognized cytokines and chemokines might act as mediators in inflammatory pain. We used ultraviolet B (UVB) irradiation to induce persistent, abnormal sensitivity to pain in humans and rats. The expression of more than 90 different inflammatory mediators was measured in treated skin at the peak of UVB-induced hypersensitivity with custom-made polymerase chain reaction arrays. There was a significant positive correlation in the overall expression profiles between the two species. The expression of several genes [interleukin-1β (IL-1β), IL-6, and cyclooxygenase-2 (COX-2)], previously shown to contribute to pain hypersensitivity, was significantly increased after UVB exposure, and there was dysregulation of several chemokines (CCL2, CCL3, CCL4, CCL7, CCL11, CXCL1, CXCL2, CXCL4, CXCL7, and CXCL8). Among the genes measured, CXCL5 was induced to the greatest extent by UVB treatment in human skin; when injected into the skin of rats, CXCL5 recapitulated the mechanical hypersensitivity caused by UVB irradiation. This hypersensitivity was associated with the infiltration of neutrophils and macrophages into the dermis, and neutralizing the effects of CXCL5 attenuated the abnormal pain-like behavior. Our findings demonstrate that the chemokine CXCL5 is a peripheral mediator of UVB-induced inflammatory pain, likely in humans as well as rats.
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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：
17.1
作者：
Dawes JM;Calvo M;Perkins JR;Paterson KJ;Kiesewetter H;Hobbs C;Kaan TK;Orengo C;Bennett DL;McMahon SB
通讯作者：
McMahon SB
影响因子：
7.4
作者：
Barclay, Jane;Clark, Anna K.;Malcangio, Marzia
通讯作者：
Malcangio, Marzia
影响因子：
--
作者：
Grespan, Renata;Fukada, Sandra Y.;Cunha, Fernando Q.
通讯作者：
Cunha, Fernando Q.
影响因子：
5.5
作者：
Cunha, Thiago M.;Verri, Waldiceu A., Jr.;Cunha, Fernando Q.
通讯作者：
Cunha, Fernando Q.