ATP receptors in pain sensation: Involvement of spinal microglia and P2X(4) receptors.
ATP receptors in pain sensation: Involvement of spinal microglia and P2X(4) receptors.
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DOI：
10.1007/s11302-005-6210-4
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发表时间：
2005-06
影响因子：
3.5
通讯作者：
Koizumi, Schuichi
中科院分区：
文献类型：
--
作者：
Inoue, Kazuhide;Tsuda, Makoto;Koizumi, Schuichi
有大量证据表明，细胞外ATP和其他核苷酸在外周和中枢神经系统的疼痛信号传导中都起着重要作用。起初，人们认为ATP仅仅与急性疼痛有关，因为ATP从受损细胞中释放出来，并通过激活初级感觉神经元的受体直接刺激它们。然而，无论是从药理学上阻断P2X/Y受体，还是从分子上抑制P2X/Y受体在感觉神经元或脊髓中的表达，对急性生理性疼痛都没有影响。目前关注的焦点是内源性ATP及其受体系统在病理性疼痛状态，特别是神经性疼痛中被激活的可能性。神经性疼痛通常是由手术、骨压迫、糖尿病或感染引起的神经损伤的结果。这种类型的疼痛非常严重，即使轻微的触摸也会引起强烈的疼痛；不幸的是，这种状态通常对现有的治疗方法有抗药性。最近的一项研究表明ATP受体（即P2X3和P2X4受体）的关键作用，在我们对神经性疼痛机制的理解方面取得了重要进展。本文综述了ATP受体，特别是P2X4受体在神经性疼痛中的作用。周围神经损伤后脊髓P2X4受体的表达在脊髓小胶质细胞中增强，药物阻断和分子抑制P2X4受体可减少神经性疼痛行为。了解ATP受体包括P2X4受体的关键作用可能会导致神经性疼痛管理的新策略。
There is abundant evidence that extracellular ATP and other nucleotides have an important role in pain signaling at both the periphery and in the CNS. At first, it was thought that ATP was simply involved in acute pain, since ATP is released from damaged cells and excites directly primary sensory neurons by activating their receptors. However, neither blocking P2X/Y receptors pharmacologically nor suppressing the expression of P2X/Y receptors molecularly in sensory neurons or in the spinal cord had an effect on acute physiological pain. The focus of attention now is on the possibility that endogenous ATP and its receptor system might be activated in pathological pain states, particularly in neuropathic pain. Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, diabetes or infection. This type of pain can be so severe that even light touching can be intensely painful; unfortunately, this state is generally resistant to currently available treatments. An important advance in our understanding of the mechanisms involved in neuropathic pain has been made by a recent work demonstrating the crucial role of ATP receptors (i.e., P2X3 and P2X4 receptors). In this review, we summarize the role of ATP receptors, particularly the P2X4 receptor, in neuropathic pain. The expression of P2X4 receptors in the spinal cord is enhanced in spinal microglia after peripheral nerve injury, and blocking pharmacologically and suppressing molecularly P2X4 receptors produce a reduction of the neuropathic pain behaviour. Understanding the key roles of ATP receptors including P2X4 receptors may lead to new strategies for the management of neuropathic pain.