Selective activation of nociceptors by P2X receptor agonists in normal and inflamed rat skin
Selective activation of nociceptors by P2X receptor agonists in normal and inflamed rat skin
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DOI：
10.1111/j.1469-7793.2001.00437.x
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发表时间：
2001-07-15
影响因子：
5.5
通讯作者：
Lewin, GR
中科院分区：
文献类型：
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作者：
Hamilton, SG;McMahon, SB;Lewin, GR
1. ATP可以在人类中引起疼痛，并且与其他P2 X通道激动剂一起可以在啮齿动物中产生伤害性反应。我们使用大鼠离体皮肤-神经制备物来量化正常和角叉菜胶炎症皮肤对ATP及其稳定类似物α，β-亚甲基ATP的初级传入反应。发现ATP和α，β-亚甲基ATP都特异性地激活皮肤中的A δ和C-纤维、伤害感受器的外周末端。百分之三十九的伤害感受器测试响应最大剂量的α，β-亚甲基ATP（5纳米）。与此相反，非伤害性，低阈值的机械敏感纤维从来没有激活相同浓度的激动剂。在伤害感受器群体中，C-机械热纤维（C-MH或多模态伤害感受器）对P2 X激动剂的反应比具有A δ-或C-纤维轴突的机械伤害感受器（C-M伤害感受器）明显更大。C-机械热和C-机械能感受器都被低至50 μ M的α，β-亚甲基ATP剂量激活。在记录前3-4小时用角叉菜胶发炎的皮肤中，响应性C纤维伤害感受器的数量和它们的响应幅度都增加。炎症条件下增加的神经反应主要在C-机械热或多模态伤害感受器中观察到。在低剂量的P2 X激动剂后，C-MH纤维而不是C-M纤维发展出升高的持续活性，并且这种作用仅在角叉菜胶炎症后观察到。研究发现，伤害感受器中α，β-亚甲基ATP诱发放电的时间过程与大鼠对先前研究中描述的相同激动剂的行为伤害反应的时间过程密切相关（汉密尔顿等人，1999）。5.我们的结论是，α，β-亚甲基ATP反应性伤害感受器数量的快速增加和角叉菜胶炎症后神经反应的幅度增加解释了为什么非常低浓度的这种激动剂可以在炎症状态下引起疼痛。
1. ATP can elicit pain in humans and, together with other P2X channel agonists, can produce nocifensive responses in rodents. We used the rat in vitro skin-nerve preparation to quantify primary afferent responses to ATP and its stable analogue alpha,beta -methylene ATP in normal and carrageenan-inflamed skin.2. Both ATP and alpha,beta -methylene ATP were found to specifically activate the peripheral terminals of A delta and C-fibre, nociceptors in the skin. Thirty-nine per cent of the nociceptors tested responded to the maximal dose of alpha,beta -methylene ATP (5 nam). In contrast, non-nociceptive, low-threshold mechano-sensitive fibres were never activated by the same agonist concentrations.3. Amongst the nociceptor population, C-mechanoheat fibres (C-MH or polymodal nociceptors) were markedly more responsive to P2X agonists than mechanonociceptors (C-M nociceptors) with A delta- or C-fibre axons. Both C-mechanoheat and C-mechanonociceptors were activated by alpha,beta -methylene ATP doses as low as 50 muM.4. In skin inflamed with carrageenan 3-4 h before recording both the number of responsive C-fibre nociceptors and their response magnitude increased. The increased neural response under inflammatory conditions was largely observed in C-mechanoheat or polymodal nociceptors. After low doses of P2X agonists C-MH fibres but not C-M fibres developed elevated ongoing activity and this effect was only seen after carrageenan inflammation. The time course of alpha,beta -methylene ATP-evoked discharges in nociceptors was found to correlate well with the time course of behavioural nocifensive responses in rats to the same agonist described in a previous study (Hamilton et al. 1999).5. We conclude that the rapid increase in the number of alpha,beta -methylene ATP responsive nociceptors and the increased magnitude of the neural response following carrageenan inflammation explains why very low concentrations of such agonists can cause pain in inflammatory states.