Brain S D, Newbold P, Kajekar R
Pharmacology Group, King's College, London, United Kingdom.
Can J Physiol Pharmacol. 1995 Jul;73(7):995-8. doi: 10.1139/y95-139.
Electrical stimulation of the sensory saphenous nerve leads to neurogenic edema formation in the innervated area of the paw of the anesthetized rat. Evidence suggests that the edema formation is the result of increased microvascular permeability mediated via neurokinin NK1 receptors and increased blood flow mediated via calcitonin gene related peptide CGRP1 receptors. Results indicate that selective receptor antagonists will only inhibit the response mediated by the specific receptor they antagonise. In the case of neurogenic inflammation, where it is common for more than one biologically active neuropeptide to be released concomitantly, it may be more sensible to develop agents that inhibit neuropeptide release. The effects of some agents suggested to affect neurogenic responses are presented. The anti-inflammatory steroid dexamethasone (1 mg/kg subcutaneously, -4 h) significantly (p < 0.01) inhibited edema formation, but the mechanism of action is likely to be related to the general anti-edema effect of dexamethasone. In contrast the anti-asthma agent nedocromil sodium (up to 10 mg/kg intravenously, -15 min) and the histamine H3 agonist (R)-alpha-methyl histamine (1-10 mg/kg intravenously, -5 min) both failed to inhibit saphenous nerve induced edema formation, despite positive results in other sensory nerve systems. The results are discussed in the context of evidence obtained using other agents in skin.
对麻醉大鼠爪部隐神经进行电刺激会导致其支配区域出现神经源性水肿。有证据表明，水肿的形成是由神经激肽NK1受体介导的微血管通透性增加以及降钙素基因相关肽CGRP1受体介导的血流增加所致。结果表明，选择性受体拮抗剂只会抑制它们所拮抗的特定受体介导的反应。在神经源性炎症中，通常会同时释放多种生物活性神经肽，因此开发抑制神经肽释放的药物可能更为明智。本文介绍了一些被认为会影响神经源性反应的药物的作用。抗炎类固醇地塞米松（皮下注射1mg/kg，-4小时）显著（p<0.01）抑制了水肿形成，但其作用机制可能与地塞米松的一般抗水肿作用有关。相比之下，抗哮喘药物奈多罗米钠（静脉注射高达10mg/kg，-15分钟）和组胺H3激动剂（R）-α-甲基组胺（静脉注射1-10mg/kg，-5分钟）尽管在其他感觉神经系统中取得了阳性结果，但均未能抑制隐神经诱导的水肿形成。本文结合使用其他药物在皮肤中获得的证据对结果进行了讨论。
