CCL-1 in the spinal cord contributes to neuropathic pain induced by nerve injury.
CCL-1 in the spinal cord contributes to neuropathic pain induced by nerve injury.
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DOI：
10.1038/cddis.2013.198
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发表时间：
2013-06-20
影响因子：
9
通讯作者：
中科院分区：
文献类型：
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作者：
已知细胞因子如白细胞介素通过激活神经胶质参与神经性疼痛的发展。然而，趋化因子（C-C基序）配体1（CCL-1），一种由活化的T细胞分泌的充分表征的趋化因子，在伤害性传递中的作用仍不清楚。我们发现，CCL-1上调后，部分坐骨神经结扎脊髓背角。因此，我们研究了重组CCL-1对行为疼痛评分、突触传递、胶质细胞功能和脊髓背角细胞因子产生的作用。在这里，我们表明，CCL-1是参与神经病理性疼痛的发展的关键介质之一。CCL-1 mRNA主要表达于同侧背根神经节，CCL-1特异性受体CCR-8在背角浅层表达上调。CCR-8的表达增加不仅在神经元中，而且在同侧的小胶质细胞和星形胶质细胞中观察到。鞘内注射重组CCL-1（i.t.）对幼稚小鼠诱导异常性疼痛，这是通过补充添加N-甲基-β-天冬氨酸（NMDA）受体拮抗剂，MK-801预防。脊髓切片的膜片钳记录显示，应用CCL-1短暂增强胶状质（板层II）的兴奋性突触传递。从长远来看，i注射CCL-1诱导脊髓中NMDA受体亚单位NR 1和NR 2B磷酸化。注射CCL-1还上调胶质细胞标志物和促炎细胞因子（IL-1β、TNF-α和IL-6）的mRNA水平。通过预防性和长期给予针对CCL-1的中和抗体和通过敲低CCR-8来减弱神经结扎引起的触觉异常性疼痛。我们的研究结果表明，CCL-1是神经病理性疼痛发病机制中的关键分子之一，CCL-1/CCR-8信号系统可能成为神经病理性疼痛治疗药物开发的潜在靶点。
Cytokines such as interleukins are known to be involved in the development of neuropathic pain through activation of neuroglia. However, the role of chemokine (C-C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, in the nociceptive transmission remains unclear. We found that CCL-1 was upregulated in the spinal dorsal horn after partial sciatic nerve ligation. Therefore, we examined actions of recombinant CCL-1 on behavioural pain score, synaptic transmission, glial cell function and cytokine production in the spinal dorsal horn. Here we show that CCL-1 is one of the key mediators involved in the development of neuropathic pain. Expression of CCL-1 mRNA was mainly detected in the ipsilateral dorsal root ganglion, and the expression of specific CCL-1 receptor CCR-8 was upregulated in the superficial dorsal horn. Increased expression of CCR-8 was observed not only in neurons but also in microglia and astrocytes in the ipsilateral side. Recombinant CCL-1 injected intrathecally (i.t.) to naive mice induced allodynia, which was prevented by the supplemental addition of N-methyl-𝒟-aspartate (NMDA) receptor antagonist, MK-801. Patch-clamp recordings from spinal cord slices revealed that application of CCL-1 transiently enhanced excitatory synaptic transmission in the substantia gelatinosa (lamina II). In the long term, i.t. injection of CCL-1 induced phosphorylation of NMDA receptor subunit, NR1 and NR2B, in the spinal cord. Injection of CCL-1 also upregulated mRNA level of glial cell markers and proinflammatory cytokines (IL-1β, TNF-α and IL-6). The tactile allodynia induced by nerve ligation was attenuated by prophylactic and chronic administration of neutralizing antibody against CCL-1 and by knocking down of CCR-8. Our results indicate that CCL-1 is one of the key molecules in pathogenesis, and CCL-1/CCR-8 signaling system can be a potential target for drug development in the treatment for neuropathic pain.
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影响因子：
56.9
作者：
Beattie, EC;Stellwagen, D;Malenka, RC
通讯作者：
Malenka, RC
影响因子：
7.4
作者：
Gao, X;Kim, HK;Chung, K
通讯作者：
Chung, K
DOI：
10.1523/jneurosci.3623-08.2009
发表时间：
2009-04-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Gao YJ;Zhang L;Samad OA;Suter MR;Yasuhiko K;Xu ZZ;Park JY;Lind AL;Ma Q;Ji RR
通讯作者：
Ji RR
DOI：
10.1177/1073858409360822
发表时间：
2010-10
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
--
作者：
Gosselin RD;Suter MR;Ji RR;Decosterd I
通讯作者：
Decosterd I
影响因子：
2.9
作者：
FUKUOKA, H;KAWATANI, M;TAKESHIGE, C
通讯作者：
TAKESHIGE, C