PROSTAGLANDINS, ASPIRIN-LIKE DRUGS AND ANALGESIA
PROSTAGLANDINS, ASPIRIN-LIKE DRUGS AND ANALGESIA
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DOI：
10.1038/newbio240200a0
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发表时间：
1972-01-01
期刊：
影响因子：
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通讯作者：
FERREIRA, SH
中科院分区：
文献类型：
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作者：
FERREIRA, SH
前列腺素在炎症中的重要性已被阿司匹林类抗炎药物抑制其合成1-3的发现所强调。这类药物的抗炎和解热作用可以在此基础上解释1，但它们的止痛特性不能与抑制前列腺素合成紧密相关。这是因为皮内注射前列腺素的唯一主观影响是温暖和轻微瘙痒*，而在水泡基底物PGE2(高达100微克/毫升)。未能产生疼痛5。现在有几篇报道描述了静脉注射前列腺素产生疼痛的活性。并给男性肌肉注射6-8支。Collier和Schneider已经证明，PGE1是在小鼠身上产生扭动反应的最强大的试剂。Vane1提示，兔主动脉收缩物质(RCS)10可能是前列腺素11生物合成过程中不稳定的环状过氧化中间体，可能参与炎症痛的产生。我试图通过比较脂肪酸氢过氧化物与高浓度的乙酰胆碱、缓激肽、组胺和前列腺素E_1在人体皮内注射时的疼痛产生活性来验证这一假设。过氧化氢引起的疼痛强度大于其他激动剂，但除PGE1外，其余均为一过性疼痛。在测试皮下注射以模拟内源性疼痛介质的持续释放时，揭示了E-型前列腺素的两个重要特性。首先，它们增加了对化学和机械刺激的疼痛敏感性。其次，它们的影响是累积的，不仅取决于它们的浓度，还取决于暴露的时间。“痛”一词是指在输液过程中化学引起的显性疼痛；当仅对输液区域施加轻微的压力而引起疼痛时，使用痛敏。研究在五名男性志愿者中进行，每个人在同意之前都得到了对实验性质的全面解释。这些实验是双盲的。
THE importance of prostaglandins in inflammation has been emphasized by the discovery that aspirin-like anti-inflammatory drugs inhibit their synthesis1–3. The anti-inflammatory and anti-pyretic effects of this group of drugs could be explained on this basis1, but their analgesic properties could not, then, be firmly linked to inhibition of prostaglandin synthesis. This was because the only subjective effect reported on intradermal injection of prostaglandin was a sensation of warmth and a slight itching*, and on the blister base PGE2(up to 100 µg/ml.) failed to produce pain5. Several reports now describe the pain-producing activity of prostaglandins infused i.v. and injected intramuscularly6–8in man. Collier and Schneider have shown that PGE1is the most powerful agent in producing writhing responses in mice9. Vane1suggested that rabbit aorta contracting substance (RCS)10which may be the unstable cyclic peroxide intermediate in the biosynthesis of prostaglandins11, may be involved in the production of pain in inflammation. I tried to test this hypothesis by comparing the pain producing activity of fatty acid hydroperoxides with that of high concentrations of acetylcholine, bradykinin, histamine and PGE1on intradermal injection in man. The intensity of the pain induced by the hydroperoxides was greater than that induced by the other agonists but for all except PGE1the pain was transitory. On testing subdermal infusions to mimic the continuous release of an endogenous mediator of pain, two important properties of E-type prostaglandins were revealed. First, they increase the pain sensitivity to chemical and mechanical stimulation. Second, their effects are cumulative and depend not only on their concentrations but also on the time of exposure. The term “pain” is used to denote the overt pain evoked chemically during the infusions; hyperalgesia is used when pain was elicited only by applying slight pressure on the infusion area. Studies were carried out in five male volunteers each of whom received a full explanation of the nature of the experiment before giving his consent. The experiments were double blind.