Painful purinergic receptors
Painful purinergic receptors
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DOI：
10.1124/jpet.106.105890
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发表时间：
2008-02-01
影响因子：
3.5
通讯作者：
Jarvis, Michael F.
中科院分区：
文献类型：
--
作者：
Donnelly-Roberts, Diana;McGaraughty, Steve;Jarvis, Michael F.
存在多种P2受体介导的机制，ATP可通过这些机制改变组织损伤后的伤害性感受敏感性。来自多种实验策略（包括遗传破坏研究和选择性拮抗剂的开发）的证据表明，P2 X受体亚型（包括P2 X（3）、P2 X（2/3）、P2 X（4）和P2 X（7）以及P2 Y（e.例如，在一个实施例中，P2 Y（2）受体，可以调节疼痛。例如，在不同的病理性疼痛动物模型中，给予选择性P2 X（3）拮抗剂A-317491已被证明能有效地阻断痛觉过敏和异常性疼痛。鞘内递送靶向P2 X（4）受体的反义寡核苷酸减少神经损伤后的触觉异常性疼痛。P2 X（7）受体的选择性拮抗剂也可降低炎症性和神经性疼痛动物模型的致敏作用，为嘌呤能神经胶质-神经相互作用是有害感觉神经传递的重要调节剂提供了证据。此外，P2 Y（2）受体的激活导致多模态瞬时受体电位-1受体的敏化。因此，ATP作用于多个嘌呤能受体，或者直接作用于神经元（例如，例如，在一个实施例中，P2 X（3）、P2 X（2/3）和P2 Y受体）或通过神经胶质细胞相互作用（P2 X（4）和P2 X（7）受体）间接改变伤害感受性。这些P2受体的选择性拮抗剂的发展极大地帮助了ATP的伤害性作用的调查。这一观点强调了一些最近的进展，以确定选择性P2受体配体，这加强了调查的ATP相关的调制疼痛敏感性。
Multiple P2 receptor-mediated mechanisms exist by which ATP can alter nociceptive sensitivity following tissue injury. Evidence from a variety of experimental strategies, including genetic disruption studies and the development of selective antagonists, has indicated that the activation of P2X receptor subtypes, including P2X(3), P2X(2/3), P2X(4) and P2X(7), and P2Y (e. g., P2Y(2)) receptors, can modulate pain. For example, administration of a selective P2X(3) antagonist, A-317491, has been shown to effectively block both hyperalgesia and allodynia in different animal models of pathological pain. Intrathecally delivered antisense oligonucleotides targeting P2X(4) receptors decrease tactile allodynia following nerve injury. Selective antagonists for the P2X(7) receptor also reduce sensitization in animal models of inflammatory and neuropathic pain, providing evidence that purinergic glial-neural interactions are important modulators of noxious sensory neurotransmission. Furthermore, activation of P2Y(2) receptors leads to sensitization of polymodal transient receptor potential-1 receptors. Thus, ATP acting at multiple purinergic receptors, either directly on neurons (e. g., P2X(3), P2X(2/3), and P2Y receptors) or indirectly through neural-glial cell interactions (P2X(4) and P2X(7) receptors), alters nociceptive sensitivity. The development of selective antagonists for some of these P2 receptors has greatly aided investigations into the nociceptive role of ATP. This perspective highlights some of the recent advances to identify selective P2 receptor ligands, which has enhanced the investigation of ATP-related modulation of pain sensitivity.