Abstract
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 intramuscularly6–8 in man. Collier and Schneider have shown that PGE1 is the most powerful agent in producing writhing responses in mice9. Vane1 suggested that rabbit aorta contracting substance (RCS)10 which 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 PGE1 on 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 PGE1 the 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.
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FERREIRA, S. Prostaglandins, Aspirin-like Drugs and Analgesia. Nature New Biology 240, 200–203 (1972). https://doi.org/10.1038/newbio240200a0
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DOI: https://doi.org/10.1038/newbio240200a0
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