Mice overexpressing chemokine ligand 2 (CCL2) in astrocytes display enhanced nociceptive responses
Mice overexpressing chemokine ligand 2 (CCL2) in astrocytes display enhanced nociceptive responses
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DOI：
10.1016/j.neuroscience.2007.08.014
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发表时间：
2007-11-09
期刊：
影响因子：
3.3
通讯作者：
Abbadie, C.
中科院分区：
文献类型：
--
作者：
Menetski, J.;Mistry, S.;Abbadie, C.
最近的研究结果表明，趋化因子，特别是CC趋化因子配体2 (CCL2或单核细胞趋化蛋白-1)，在疼痛加工中起着重要作用。在本研究中，我们评估了在神经胶质纤维酸性蛋白启动子（CCL2 tg）控制下过表达CCL2的小鼠的伤害性反应。在急性伤害感觉模型中，CCL2 tg小鼠在对热（热板）和化学（福尔马林试验）刺激方式的反应中表现出与野生型对照相比显著增强的伤害行为。在部分坐骨神经结扎模型中，机械异常性疼痛在异常性反应的大小或持续时间方面没有差异；但两组均有最大可测程度的反应。在足底注射完全弗氏佐剂（CFA）引起的炎症性疼痛模型中，与对照组小鼠相比，CCL2 tg小鼠表现出更大的水肿和热痛觉过敏。在对照小鼠中，水肿和痛觉过敏在CFA后5-7天恢复到基线值。然而，在CCL2 tg小鼠中，CFA后3周的热痛觉过敏与基线有显著差异。与这些增强的行为反应并行，CCL2过表达小鼠的CCL2血清水平显著升高，并在CFA后7天保持升高。因此，促炎细胞因子mRNA （IL-1 β、IL-6和TNF α）在皮肤、背根神经节（DRG）和脊髓中的表达水平较高，而抗炎细胞因子（IL-10）在CCL2过表达小鼠皮肤和DRG中的表达水平低于对照小鼠。结合来自CCR2缺失小鼠的数据，这些数据证实了CCL2/CCR2轴在疼痛通路中的关键作用，并表明抑制该轴可能导致新的疼痛治疗。(c) 2007 ibro。Elsevier Ltd.出版。版权所有。
Recent findings demonstrate that chemokines, and more specifically CC chemokine ligand 2 (CCL2 or monocyte chemoattractant protein-1), play a major role in pain processing. In the present study, we assess nociceptive responses of mice that overexpressed CCL2 under control of glial fibrillary acidic protein promoter (CCL2 tg). In models of acute nociception CCL2 tg mice demonstrated significantly enhanced nociceptive behavior relative to wild-type controls in responses to both thermal (hot plate) and chemical (formalin test) stimulus modalities. There were no differences in mechanical allodynia in the partial sciatic nerve ligation model, in terms of either magnitude or duration of the allodynic response; however, both groups responded to the maximal extent measurable. In a model of inflammatory pain, elicited by intraplantar administration of complete Freund's adjuvant (CFA), CCL2 tg mice displayed both greater edema and thermal hyperalgesia compared with control mice. In control mice, edema and hyperalgesia returned to baseline values 5-7 days post CFA. However, in CCL2 tg mice, thermal hyperalgesia was significantly different from baseline up to 3 weeks post CFA. Parallel to these enhanced behavioral responses CCL2 serum levels were significantly greater in CCL2 overexpressing mice and remained elevated 7 days post CFA. Consequently, proinflarnmatory cytokine mRNA expression (IL-1 beta, IL-6, and TNF alpha) levels were greater in skin, dorsal root ganglia (DRG), and spinal cord, whereas the anti-inflammatory cytokine (IL-10) level was lower in skin and DRG in CCL2 overexpressing mice than in control mice. Taken together with data from CCR2-deficient mice, these present data confirm a key role of CCL2/CCR2 axis in pain pathways and suggest that inhibiting this axis may result in novel pain therapies. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.