Acute and chronic phases of complex regional pain syndrome in mice are accompanied by distinct transcriptional changes in the spinal cord.
Acute and chronic phases of complex regional pain syndrome in mice are accompanied by distinct transcriptional changes in the spinal cord.
复制标题
小鼠复杂区域疼痛综合征的急性和慢性阶段伴随着脊髓的不同转录变化。
DOI：
10.1186/1744-8069-9-40
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发表时间：
2013-08-08
期刊：
影响因子：
3.3
通讯作者：
Clark JD
中科院分区：
文献类型：
--
作者：
Gallagher JJ;Tajerian M;Guo T;Shi X;Li W;Zheng M;Peltz G;Kingery WS;Clark JD
CRPS是一种疼痛、虚弱且通常是慢性的疾病，其特征是各种感觉、运动和血管障碍。尽管进行了多年的研究，但目前的治疗方法受到我们对潜在机制的理解的限制。对于支持通常在CRPS肢体中观察到的伤害性敏感性的基因表达的变化，或者这些变化如何随着时间的推移而演变，在分子水平上知之甚少。我们使用一种具有良好特征的小鼠胫骨骨折/石膏固定CRPS模型来研究分子、血管和伤害性变化。我们观察到，在我们的模型中，CRPS样改变的急性(骨折后3周)和慢性(骨折后7周)阶段伴随着与不同典型路径相对应的独特的脊髓基因表达变化。急性期调节最多的通路是：趋化因子信号、糖原降解和cAMP介导的信号；慢性期调节最多的通路是凝血系统、颗粒酶A信号和芳烃受体信号。然后我们重点研究了CCL2的作用，这是一种趋化因子，在我们的模型中，脊髓组织中的mRNA和蛋白质水平上调了CCL2。我们通过证明在CRPS动物的脊髓而不是外周给药CCR2拮抗剂(RS504393)可以减少机械性痛觉异常，从而证实了它与这个模型中显示的伤害性敏化的相关性。脊髓注射CCL2本身可引起对照组小鼠的机械性痛觉异常。我们的数据提供了在小鼠模型中伴随CRPS急性期和慢性期脊髓转录变化的全球观察。此外，它还跟踪了CCL2编码的最高调控基因之一，并验证了它在CRPS骨折/石膏模型中调节伤害性感觉的作用。
CRPS is a painful, debilitating, and often-chronic condition characterized by various sensory, motor, and vascular disturbances. Despite many years of study, current treatments are limited by our understanding of the underlying mechanisms. Little is known on the molecular level concerning changes in gene expression supporting the nociceptive sensitization commonly observed in CRPS limbs, or how those changes might evolve over time. We used a well-characterized mouse tibial fracture/cast immobilization model of CRPS to study molecular, vascular and nociceptive changes. We observed that the acute (3 weeks after fracture) and chronic (7 weeks after fracture) phases of CRPS-like changes in our model were accompanied by unique alterations in spinal gene expression corresponding to distinct canonical pathways. For the acute phase, top regulated pathways were: chemokine signaling, glycogen degradation, and cAMP-mediated signaling; while for the chronic phase, the associated pathways were: coagulation system, granzyme A signaling, and aryl hydrocarbon receptor signaling. We then focused on the role of CcL2, a chemokine that we showed to be upregulated at the mRNA and protein levels in spinal cord tissue in our model. We confirmed its association with the nociceptive sensitization displayed in this model by demonstrating that the spinal but not peripheral administration of a CCR2 antagonist (RS504393) in CRPS animals could decrease mechanical allodynia. The spinal administration of CcL2 itself resulted in mechanical allodynia in control mice. Our data provide a global look at the transcriptional changes in the spinal cord that accompany the acute and chronic phases of CRPS as modeled in mice. Furthermore, it follows up on one of the top-regulated genes coding for CcL2 and validates its role in regulating nociception in the fracture/cast model of CRPS.
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影响因子：
7.4
作者：
Kalliomaki, Jarkko;Attal, Nadine;Bouhassira, Didier
通讯作者：
Bouhassira, Didier
DOI：
10.1523/jneurosci.0485-09.2009
发表时间：
2009-06-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Jung H;Bhangoo S;Banisadr G;Freitag C;Ren D;White FA;Miller RJ
通讯作者：
Miller RJ
影响因子：
3.3
作者：
Alvarado S;Tajerian M;Millecamps M;Suderman M;Stone LS;Szyf M
通讯作者：
Szyf M
影响因子：
15.1
作者：
Alexander, Guillermo M.;Perreault, Marielle J.;Schwartzman, Robert J.
通讯作者：
Schwartzman, Robert J.
影响因子：
7.4
作者：
Li WW;Guo TZ;Liang D;Shi X;Wei T;Kingery WS;Clark JD
通讯作者：
Clark JD