TOPICAL ACETYLSALICYLIC, SALICYLIC-ACID AND INDOMETHACIN SUPPRESS PAIN FROM EXPERIMENTAL TISSUE ACIDOSIS IN HUMAN SKIN

Topically applied acetylsalicylic acid (ASA), salicylic acid (SA) and indomethacin were tested in an experimental pain model that provides d irect nociceptor excitation through cutaneous tissue acidosis. In 30 v olunteers, sustained burning pain was produced in the palmar forearm t hrough a continuous intradermal pressure infusion of a phosphate-buffe red isotonic solution (pH 5.2). In 5 different, double-blind, randomiz ed cross-over studies with 6 volunteers each, the flow rate of the syr inge pump was individually adjusted to result in constant pain ratings of around 20% (50% in study 4) on a visual analog scale (VAS). The pa inful skin area was then covered with either placebo or the drugs whic h had been dissolved in diethylether. In the first study on 6 voluntee rs, ASA (60 mg/ml) or lactose (placebo) in diethylether (10 ml) was ap plied, using both arms at 3-day intervals. Both treatments resulted in sudden and profound pain relief due to the cooling effect of the evap orating ether. With lactose, however, the mean pain rating was restore d close to the baseline within 6-8 min while, with ASA, it remained si gnificantly 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 m g/ml) and SA (60 mg/ml) were equally effective as ASA (each 92-96% pai n reduction) and that the antinociceptive effects were due to focal bu t not systemic actions, since ASA and SA did not reach measurable plas ma levels up to 3 h after topical applications. With a higher flow rat e of acid buffer producing more intense pain (VAS 50%), ASA and SA wer e still able to significantly reduce the ratings by 90% or 84%, respec tively. 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 competitiv e mechanism of (acetyl-) salicylic antinociception.