Relief of inflammatory pain in rats by local use of the selective P2X7 ATP receptor inhibitor, oxidized ATP
Relief of inflammatory pain in rats by local use of the selective P2X7 ATP receptor inhibitor, oxidized ATP
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DOI：
10.1002/art.10678
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发表时间：
2002-12-01
影响因子：
--
通讯作者：
Ferrero, ME
中科院分区：
文献类型：
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作者：
Dell'Antonio, G;Quattrini, A;Ferrero, ME
Objective.氧化型ATP（oATP）是细胞外ATP的P2 Z/P2 X7 ATP受体的选择性抑制剂，其有助于抗伤害感受效应。本研究旨在确定局部给药oATP能够缓解关节炎大鼠足的炎性疼痛的机制。通过将弗氏完全佐剂注射到Wistar大鼠的一只后爪中来诱导关节炎。在将oATP局部注射到发炎的爪中之前和之后测量伤害感受阈值。由于在炎症部位存在募集的炎性细胞而对疼痛传递的影响通过抑制其迁移的初始阶段来确定（通过用岩藻多糖静脉内治疗，其阻断选择素家族的粘附分子）。在不同的实验条件下测定足底ATP含量。用抗P2 X7受体多克隆抗体评价后爪的组织学特征。足底内给药oATP到发炎的爪子显着缓解炎症疼痛。oATP的抗伤害效应不依赖于免疫细胞的募集。oATP治疗显著降低了炎症组织中的ATP水平。观察到皮肤感觉神经上的P2 X7受体相对于不同治疗的可变存在。oATP处理后，外周神经末梢和内皮细胞中P2 X7的表达减少。氧化ATP通过抑制位于神经末梢的ATP的P2 X7受体来抑制关节炎大鼠的炎性疼痛。
Objective. Oxidized ATP (oATP) is a selective inhibitor of the P2Z/P2X7 ATP receptor for extracellular ATP, which contributes to the antinociceptive effect. This study sought to determine the mechanism by which local administration of oATP is able to relieve inflammatory pain in arthritic rat paws.Methods. Arthritis was induced in Wistar rats by injections of Freund's complete adjuvant into one hind paw. Nociceptive thresholds were measured before and after local injection of oATP into the inflamed paws. The influence on pain transmission due to the presence of recruited inflammatory cells at the site of inflammation was determined by inhibiting the initial phase of their migration (by intravenous treatment with fucoidin, which blocks the adhesion molecules of the selectin family). ATP intraplantar content was determined in the different experimental conditions. Histologic features of the hind paws were evaluated by using the anti-P2X7 receptor polyclonal antibody.Results. Intraplantar administration of oATP into inflamed paws significantly relieved inflammatory pain. The antinociceptive effect of oATP was independent of the immune-cell recruitment. ATP levels in inflamed tissues were significantly reduced by oATP treatment. A variable presence of P2X7 receptors on cutaneous sensory nerves with respect to the different treatments was observed. Following oATP treatment, there was a reduction in P2X7 expression in the endings of peripheral nerves, as well as in endothelial cells.Conclusion. Oxidized ATP inhibits inflammatory pain in arthritic rats by inhibition of the P2X7 receptor for ATP, which is localized on nerve terminals.