Periodate oxidized ATP (oATP) reduces hyperalgesia in mice: Involvement of P2X7 receptors and implications for therapy
Periodate oxidized ATP (oATP) reduces hyperalgesia in mice: Involvement of P2X7 receptors and implications for therapy
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DOI：
10.1177/039463200802100108
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发表时间：
2008-01-01
影响因子：
3.5
通讯作者：
Ferrero, M. E.
中科院分区：
文献类型：
--
作者：
Fulgenzi, A.;Ticozzi, P.;Ferrero, M. E.
一些炎症介质不仅在炎症性疼痛的发病机制中起重要作用，而且在神经病理性疼痛和内脏疼痛的发病机制中也起重要作用。我们先前在实验性炎症中显示了oATP的抗痛觉过敏作用，oATP是亲伤害性ATP的P2X7受体的抑制剂。在这里，我们展示了oATP在小鼠神经性和内脏疼痛模型中的抗痛觉过敏作用，而不是在模拟人类类风湿性关节炎的关节炎疼痛模型中。我们还表明，缺乏P2X7受体（KO）的小鼠在诱导关节炎性疼痛、神经性疼痛和内脏疼痛后对痛觉过敏性热刺激具有抗性。用oATP局部（注射到右后爪中）预处理能够防止野生型小鼠中ATP依赖性痛觉过敏的连续诱导。此外，KO小鼠对用ATP的足底内治疗不敏感。我们的数据表明，即使oATP能够抑制不同于P2X7的嘌呤受体，后者在疼痛传递中的作用更重要。
Some inflammatory mediators play an important role not only in the pathogenesis of the inflammatory pain, but also in that of neuropathic and visceral pain. We previously showed the antihyperalgesic effect of oATP, the inhibitor of the P2X7 receptors for the pro-nociceptive ATP, in experimental inflammation. Here we show the antihyperalgesic effect of oATP in mouse models of neuropathic and visceral pain, other than in a model of arthritic pain mimicking rheumatoid arthritis in humans. We also show that mice lacking P2X7 receptors (KO) are resistant to hyperalgesic thermal stimuli following the induction of arthritic, neuropathic and visceral pain. Local (injection into the right hind paw) pre-treatment with oATP is able to prevent the successive induction of ATP-dependent hyperalgesia in wild type mice. In addition, KO mice are not insensitive to intraplantar treatment with ATP. Our data suggest that, even if oATP is able to inhibit purinoceptors different from P2X7, the latter are the more important involved in pain transmission.