Acetylsalicylic acid reduces pH-induced excitation of rat cutaneous nociceptors in vitro

Abstract

The effects of acetylsalicylic acid (ASA) and of salicylic acid (SA) on pH-induced nociceptor excitation were investigated in a rat skin-saphenous nerve preparation in vitro, where isolated receptive fields of identified single nerve fibers were superfused at the corium side with controlled solutions to test their chemosensitivity. A total of 133 unmyelinated mechano-heat-sensitive ('polymodal') C-fibers were superfused with an acidic solution (CO2-saturated synthetic interstitial fluid; pH 6.1) for at least 10 min. If fibers responded to the acid pH (n=89; 67%), ASA or SA was added after 10 min for a 10 min period in various concentrations (ASA: 10-5 up to 10-3 M; SA: 10-7 up to 10-3 M), and the pH stimulation was continued for at least another 15 min. In most cases, only one substance was applied at one concentration per fiber. A bell-shaped dose-response curve of reversible, weak effects on pH-induced discharge resulted from SA, with a maximum effect at 10-5 M (14% suppression, n=16, P<0.01); at 10-3 M an excitatory action of SA in acidic solution became apparent (17% increase in discharge, n=9, P= NS). The application of freshly dissolved ASA led to a linear dose-response curve, with a significant reduction in discharge rate (10-4 M: 12.4%, n=11, P<0.02; 10-3 M: 42%, n=10, P<0.03). The major reduction was irreversible within at least 26 min of wash-out. Before and after each experiment, the threshold to punctuate mechanical stimulation (von Frey) was determined and found not to be significantly altered with both ASA and SA. Plasma concentrations in the 10-4 M range are normally reached with therapeutic ASA doses and much higher concentrations have to be expected in acidic tissues. Our results may, thus, help to explain aspirin's antinociceptive action. The role of prostaglandin synthesis inhibition is discussed.