Contributions of arachidonic acid derivatives and substance P to the sensitization of cutaneous nociceptors.

Contributions of arachidonic acid derivatives and substance P to the sensitization of cutaneous nociceptors.
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DOI:
10.1152/jn.1990.64.2.457
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发表时间:
1990-08
影响因子:
2.5
通讯作者:
R. Cohen;E. Perl
R. Cohen;E. Perl
中科院分区:
医学3区
文献类型:
--
作者:
R. Cohen;E. Perl

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1.假定的化学介质的炎症在热诱导的皮肤C-多模态伤害感受器(CPNs)的敏感性的作用进行了研究,在兔耳制备维持在体外动脉灌注的溶液中的蛋白质和细胞元素。2.在这种制备中,CPNs在反复暴露于有害水平的热后始终表现出增强的反应性。致敏的平均幅度在数量上与体内观察到的相似,这表明血源性因子对致敏的发展并不重要。3.当灌流液含有环氧合酶抑制剂消炎痛或安乃近或环氧合酶/脂氧合酶双重抑制剂BW 755 C时,随机选择的一半CPN的致敏作用被阻断或降低,尽管对热和压力的初始反应性没有改变。这些观察结果表明,花生四烯酸分解产物,可能是花生四烯酸,是一些,但不是全部,皮肤的C-纤维伤害感受器的敏化的中间体。此外,一些C-纤维皮肤伤害感受器的热诱导敏化是至少部分独立于参与激发的过程的结果。4. P物质(SP)或假定的SP拮抗剂,[D-Pro 2,D-Trp 7.9]-SP或[D-Pro 2,D-Phe 7,D-Trip 9]-SP,对热反应性或致敏性没有显著影响,尽管重复热刺激后持续的活性可能略高于对照水平。我们的结论是,SP在体外制备不参与增强皮肤C-纤维伤害性感受器反应后,反复热损伤。
1. The role of presumed chemical mediators of inflammation in the heat-induced sensitization of cutaneous C-polymodal nociceptors (CPNs) was examined in a rabbit ear preparation maintained in vitro by intra-arterial perfusion with a solution free of protein and cellular elements. 2. In this preparation, CPNs consistently showed enhanced responsiveness after repeated exposure of their receptive fields to noxious levels of heat. The average magnitude of sensitization was quantitatively similar to that observed in vivo, suggesting that blood-born factors are not essential for development of sensitization. 3. Sensitization in one-half of randomly selected CPNs was blocked or reduced when the perfusate contained a cyclooxygenase inhibitor, indomethacin or dipyrone, or the dual cyclooxygenase/lipoxygenase inhibitor, BW755C, even though initial responsiveness to heat and pressure was unaltered. These observations suggest that arachidonic acid breakdown products, possibly prostaglandins, are intermediaries in the sensitization of some, but not all, C-fiber nociceptors of the skin. In addition, heat-induced sensitization for some C-fiber cutaneous nociceptors is the result of processes that are at least partially independent of those involved in excitation. 4. Substance P (SP) or the putative SP antagonists, [D-Pro2, D-Trp7.9]-SP or [D-Pro2, D-Phe7, D-Trip9]-SP, produced no significant effect on heat-responsiveness or sensitization, although ongoing activity may have marginally increased over control levels after repeated heat stimulations. We conclude that SP in an in vitro preparation is not involved in the enhancement of cutaneous C-fiber nociceptor responsiveness after repeated thermal insults.