Mayer Steffi, Izydorczyk Iwona, Reeh Peter W, Grubb Blair D
Department of Physiology and Pathophysiology, Friedrich-Alexander-University of Erlangen-Nuremberg, Universitaetsstr. 17, D-91054 Erlangen, Germany.
Pain. 2007 Jul;130(1-2):14-24. doi: 10.1016/j.pain.2006.10.027. Epub 2006 Dec 28.
Bradykinin is an important inflammatory mediator that can either activate and/or sensitise nociceptors to heat stimuli applied to the skin. Several studies have suggested that prostaglandins and thus the cyclooxygenase (cox) enzymes are important in the sensitisation process but little is known about the relative involvement of the two cox isoforms, cox-1 and cox-2. Extracellular recordings were made from C-mechanoheat-sensitive fibres in isolated rat skin-saphenous nerve preparations. Bradykinin-mediated sensitisation of heat responses in these afferents was significantly attenuated by the selective cox-1 inhibitor, SC-560, and by the selective cox-2 inhibitor, NS-398. In the same experiments, bradykinin-mediated induction of ongoing activity was reduced by SC-560 but not NS-398. In a second series of experiments, bradykinin-stimulated synthesis and release of prostaglandin E2 (PGE2) was measured in isolated skin-nerve preparations. Although the basal release of PGE2 appeared unaffected by either drug, bradykinin-stimulated PGE2 release from the skin was inhibited by both SC-560 and NS-398. Immunocytochemical evaluation revealed cox-1 immunostaining was present in large cutaneous nerve branches, small intradermal nerve bundles as well as nerve endings within the skin. Cox-1 labelling was also present in non-neuronal cell types such as mast cells. Cox-2 immunoreactivity was weak but where present was located in small nerve bundles, smaller intradermal nerve bundles and nerve endings. This study shows that both cox isoforms are present in skin and that they have an important role in mediating bradykinin-evoked heat sensitisation of C-MH sensitive fibres through cox-1 and cox-2 dependent prostaglandin synthesis.
缓激肽是一种重要的炎症介质，它可以激活和/或使伤害感受器对施加于皮肤的热刺激敏感。多项研究表明，前列腺素以及环氧化酶（COX）在该致敏过程中起重要作用，但对于两种COX同工型COX-1和COX-2的相对参与情况知之甚少。在分离的大鼠皮肤-隐神经标本中，对C型机械热敏感纤维进行了细胞外记录。选择性COX-1抑制剂SC-560和选择性COX-2抑制剂NS-398可显著减弱这些传入纤维中缓激肽介导的热反应致敏作用。在同一实验中，SC-560可降低缓激肽介导的持续性活动诱导，但NS-398则无此作用。在第二系列实验中，在分离的皮肤-神经标本中测量了缓激肽刺激的前列腺素E2（PGE2）合成和释放。尽管两种药物似乎均未影响PGE2的基础释放，但SC-560和NS-398均可抑制缓激肽刺激的皮肤PGE2释放。免疫细胞化学评估显示，COX-1免疫染色存在于大的皮神经分支、小的皮内神经束以及皮肤内的神经末梢中。COX-1标记也存在于非神经元细胞类型中，如肥大细胞。COX-2免疫反应性较弱，但在存在的情况下位于小神经束、较小的皮内神经束和神经末梢中。本研究表明，两种COX同工型均存在于皮肤中，并且它们在通过COX-1和COX-2依赖性前列腺素合成介导缓激肽诱发的C-MH敏感纤维热致敏中起重要作用。
