title: Topical acetylsalicylic, salicylic acid and indomethacin suppress pain from experimental tissue acidosis in human skin.
abstract: Topically applied acetylsalicylic acid (ASA), salicylic acid (SA) and indomethacin were tested in an experimental pain model that provides direct nociceptor excitation through cutaneous tissue acidosis. In 30 volunteers, sustained burning pain was produced in the palmar forearm through a continuous intradermal pressure infusion of a phosphate-buffered isotonic solution (pH 5.2). In 5 different, double-blind, randomized cross-over studies with 6 volunteers each, the flow rate of the syringe pump was individually adjusted to result in constant pain ratings of around 20% (50% in study 4) on a visual analog scale (VAS). The painful skin area was then covered with either placebo or the drugs which had been dissolved in diethylether. In the first study on 6 volunteers, ASA (60 mg/ml) or lactose (placebo) in diethylether (10 ml) was applied, using both arms at 3-day intervals. Both treatments resulted in sudden and profound pain relief due to the cooling effect of the evaporating ether. With lactose, however, the mean pain rating was restored close to the baseline within 6-8 min while, with ASA, it remained significantly depressed for the rest of the observation period (another 20 min). This deep analgesia was not accompanied by a loss of tactile sensation. The further studies served to show that indomethacin (4.5 mg/ml) and SA (60 mg/ml) were equally effective as ASA (each 92-96% pain reduction) and that the antinociceptive effects were due to local but not systemic actions, since ASA and SA dis not reach measurable plasma levels up to 3 h after topical applications. With a higher flow rate of acid buffer producing more intense pain (VAS 50%). ASA and SA were still able to significantly reduce the ratings by 90% or 84%, respectively. On the other hand, by increasing the flow rate by a factor of 2 on average, during the period of fully developed drug effect it was possible to overcome the pain suppression, which suggests a competitive mechanism of (acetyl-) salicylic antinociception.
authors.affiliation: Universitäts-Hautklinik und Poliklinik der Universität Bonn, D-53105 Bonn, Germany Institut für Physiologie und Experimentelle Pathophysiologie Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany.
authors.forename: Kay H
authors.initials: KH
authors.lastname: Steen
authors.forename: Peter W
authors.initials: PW
authors.lastname: Reeh
authors.forename: Hans W
authors.initials: HW
authors.lastname: Kreysel
mesh_terms: D000138:Acidosis / Q000139:chemically induced / Q000188:drug therapy*; D000287:Administration, Topical; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage*; D007271:Injections, Intradermal; D007552:Isotonic Solutions / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D011312:Pressure; D012459:Salicylates / Q000008:administration & dosage*; D020156:Salicylic Acid; D012871:Skin Diseases / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D007552:Isotonic Solutions; D012459:Salicylates; D020156:Salicylic Acid; D001241:Aspirin; D007213:Indomethacin