Biochemical and pharmacological assessment of MAP-kinase signaling along pain pathways in experimental rodent models: a potential tool for the discovery of novel antinociceptive therapeutics
Biochemical and pharmacological assessment of MAP-kinase signaling along pain pathways in experimental rodent models: a potential tool for the discovery of novel antinociceptive therapeutics
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DOI：
10.1016/j.bcp.2013.11.019
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发表时间：
2014-02-01
影响因子：
5.8
通讯作者：
Bitner, Robert S.
中科院分区：
文献类型：
--
作者：
Edelmayer, Rebecca M.;Brederson, Jill-Desiree;Bitner, Robert S.
外周或中枢神经系统的损伤可诱导神经组织内的变化，从而促进可能是病理性慢性疼痛的基础的致敏状态。与慢性疼痛相关的外周和中枢神经元致敏的启动和维持中的关键生化事件是促分裂原活化蛋白激酶（MAPK）和立即早期基因转录因子（特别是cAMP反应元件结合蛋白（CREB））的磷酸化和随后的活化。在这篇评论中，我们回顾了临床前的数据，描述解剖和机制方面的伤害性感受诱导的信号沿着伤害性感受通路，包括外周皮肤轴突，背根神经节，脊髓背角和大脑皮层。除了伤害性信号传导的区域表现之外，研究还试图阐明生物化学伤害性处理的细胞起源，其中通信，即神经元和神经胶质之间的串扰被视为致病性疼痛发展的重要组成部分。在这里，我们概述了一种研究策略，通过该策略，在实验性疼痛模型中，伤害性感受诱导的细胞信号传导，特别是MAPK和CREB磷酸化，可以用来提供药物-靶点相互作用的机制洞察沿着伤害性感受途径。我们描述了一系列的研究，使用伤害性炎症和神经性疼痛模型，以调查已知的疼痛治疗对伤害性诱导的生化信号传导的影响，并提出这作为一个补充的研究策略，用于评估抗伤害性活性在临床前开发的新的疼痛治疗。(C)2013 Elsevier Inc. All rights reserved.
Injury to the peripheral or central nervous system can induce changes within the nervous tissues that promote a state of sensitization that may underlie conditions of pathological chronic pain. A key biochemical event in the initiation and maintenance of peripheral and central neuronal sensitization associated with chronic pain is the phosphorylation and subsequent activation of mitogen-activated protein kinases (MAPKs) and immediate early gene transcription factors, in particular cAMP-response element binding protein (CREB). In this commentary we review the preclinical data that describe anatomical and mechanistic aspects of nociceptive-induced signaling along nociceptive pathways including peripheral cutaneous axons, the dorsal root ganglia, spinal cord dorsal horn and cerebral cortex. In addition to the regional manifestation of nociceptive signaling, investigations have attempted to elucidate the cellular origin of biochemical nociceptive processing in which communication, i.e. crosstalk between neurons and glia is viewed as an essential component of pathogenic pain development. Here, we outline a research strategy by which nociceptive-induced cellular signaling in experimental pain models, specifically MAPK and CREB phosphorylation can be utilized to provide mechanistic insight into drug-target interaction along the nociceptive pathways. We describe a series of studies using nociceptive inflammatory and neuropathic pain models to investigate the effects of known pain therapeutics on nociceptive-induced biochemical signaling and present this as a complementary research strategy for assessing antinociceptive activity useful in the preclinical development of novel pain therapeutics. (C) 2013 Elsevier Inc. All rights reserved.