Clinical Rheumatology

, Volume 17, Issue 1, pp 17–25 | Cite as

The early clinical history of salicylates in rheumatology and pain

  • T. Hedner
  • B. Everts
Original Article


The first clinical reports on the treatment of fever and pain with salicylate-containing natural willow bark remedies were made by the English clergyman Edward Stone in 1763. The pharmacologically active principles were isolated from natural sources by Italian, German and French scientists between 1826 and 1829. Salicylic acid was first synthesised by the German Gerland in 1852 and a year later the Frenchman Gerhardt synthesised acetylsalicylic acid. The first reports on the clinical use of salicylic acid in rheumatic disorders were made independently by the two German physicians Stricher and Reiss in 1876. Acetylsalicylic acid was rediscovered by Hoffmann in 1897 and by the turn of the century it had gained worldwide recognition in the treatment of pain and rheumatological disorders. Reports on adverse events relating to gastrointestinal intolerance and bleeding appeared early, but were largely neglected until the 1950s. Today, salicylates are still widely used as analgesic, antipyretic and anti-inflammatory drugs. New indications, such as thrombosis prophylaxis, have emerged during the last decades, and yet others are being explored.

Key words

History Pain Rheumatology Salicylates 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gross M, Greenberg LA. The salicylates: a critical bibliographic review. New Haven, CT: Hillhouse Press, 1948:1–8.Google Scholar
  2. 2.
    Stone E. An account of the success of the bark of the willow in the cure of agues. Philos Trans R Soc Lond [Biol] 1763;53:195–200.Google Scholar
  3. 3.
    Bywaters EGL. The history of salicylate. In: Dixon ASJ, Smith MJ, Martin BK, Wood PNH, editors. Salicylates: an international symposium. London: J & A Churchill, 1963:3–4Google Scholar
  4. 4.
    Schindler PE: Aspirin therapy. New York: Walker and Co. 1978:1–34.Google Scholar
  5. 5.
    Weissmann G. Aspirin. Sci Am 1991;264:84–90.Google Scholar
  6. 6.
    Collier HOJ, Aspirin. Sci Am 1963;209:98–108.Google Scholar
  7. 7.
    Mann CC, Plummer ML: The aspirin wars: money medicine and 100 years of rampant competition. New York: Alfred A Knopf, 1991:1–420.Google Scholar
  8. 8.
    Mueller RL, Scheidt S. History of drugs for thrombotic disease. Discovery, development and directions for the future. Circulation 1994:89:432–49.PubMedGoogle Scholar
  9. 9.
    Stricker F. Aus der Traubschen Klinik. Ueber die Resultate der behandlung der polyarthritis rheumatica mit Salicylsäure. Berl Klin Woschr 1876;13:1–2, 8, 13, 15.Google Scholar
  10. 10.
    Maclagan T. The treatment of acute rheumatism by salicin. Lancet 1876;1:342–343, 383–384.Google Scholar
  11. 11.
    Tainter ML, Ferris AJ. Aspirin in modern therapy: a review. New York: Bayer, 1969:5–7.Google Scholar
  12. 12.
    Dreser H. Pharmakologisches untersuchung uber aspirin (acetylsalicylsäure). Pflugers Arch 1899;76:6–318.Google Scholar
  13. 13.
    Witthauer K. Aspirin, ein neues Salicylpräparat. Die Heilkunde 1899;3:396–8.Google Scholar
  14. 14.
    Wohlgemuth J. Ueber Aspirin (Acetylsalicysäure). Therap Monatshefte 1899;3:276–8.Google Scholar
  15. 15.
    Binz C. Ueber wirkung der salicylsäure auf die gessärmutter. Berl Klin Woschr 1893;30:85–87.Google Scholar
  16. 16.
    Douthwaite AH, Lintott SAM. Gastroscopic observation of the effect of aspirin and certain other substances on the stomach. Lancet 1938;2:1222–5.Google Scholar
  17. 17.
    Gillies M, Skyring A. Gastric ulcer, duodenal ulcer and gastric carcinoma: a case-control study of certain social and environmental factors. Med J Aust 1968;2:1132–6.PubMedGoogle Scholar
  18. 18.
    Sun DC, Roth SH, Mitchell CS, Englund DW. Upper gastrointestinal disease in rheumatoid arthritis. Am J Dig Dis 1974;19:405–10.PubMedGoogle Scholar
  19. 19.
    Levy M. Aspirin use in patients with major upper gastrointestinal bleeding and peptic ulcer disease: a report from the Boston Collaborative Drug Surveillance Program. N Engl J Med 1974;290:1159–62Google Scholar
  20. 20.
    Insel PA. Analgesic, antipyretics and antiinflammatory agents: drugs employed in the treatment of rheumatoid arthritis and gout. In: Gilman AG, Rall TW, Nies AS, Taylor P, editors. The pharmacological basis of therapeutics. 8th ed. Tarrytown, NY: Pergamon, 1990:638–81.Google Scholar
  21. 21.
    Link KP, Overman RS, Sullivan WR, Huebner CF, Scheel LD. Studies on hemorrhagic sweet clover disease: hypoprothrombinemia in rat induced by salicylic acid. J Biol Chem 1943;147–63.Google Scholar
  22. 22.
    Goven CD. The effect of salicylate administration on the prothrombin time. J Pediatr 1946;29:629–36.Google Scholar
  23. 23.
    Gibson PC. Salicylic acid for coronary thrombosis? Lancet 1948;1:965.Google Scholar
  24. 24.
    Gibson PC. Aspirin in the treatment of vascular disease. Lancet 1949;2:1172–4.PubMedGoogle Scholar
  25. 25.
    Craven LL. Acetylsalicylic acid, possible preventive of coronary thrombosis. Ann West Med Surg 1950;4:95.PubMedGoogle Scholar
  26. 26.
    Craven LL. Experiences with aspirin (acetylsalicylic acid) in the nonspecific prophylaxis of coronary thrombosis. Miss Valley Med J 1953;75:38–40.PubMedGoogle Scholar
  27. 27.
    Craven LL. Prevention of conronary and cerebral thrombosis. Miss Valley Med J 1956;78:213–5.PubMedGoogle Scholar
  28. 28.
    Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature 1971;231:232–5.Google Scholar
  29. 29.
    Herchman HR. Prostaglandin synthetase 2. Biochim Biophys Acta 1996;1299:125–40.PubMedGoogle Scholar

Copyright information

© Clinical Rheumatology 1988

Authors and Affiliations

  1. 1.Department of Clinical PharmacologySahlgrenska University HospitalGöteborgSweden

Personalised recommendations