EFFECTS OF INTRAVENOUS NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON A C-FIBER REFLEX ELICITED BY A WIDE-RANGE OF STIMULUS INTENSITIES IN THE RAT

A C-fiber reflex elicited by electrical stimulation within the territo ry of the sural nerve, was recorded from the ipsilateral biceps femori s muscle in anesthetized rats, The temporal evolution of the response was studied using a constant stimulus intensity (3 x threshold) and re cruitment curves were built by varying stimulus intensity from 0 to 7 x threshold. The i.v. administration of aspirin, indomethacin, ketopro fen, paracetamol (= acetaminophen) and lysine clonixinate resulted in dose-dependent depressions of the C-fiber reflex by up to 30 to 40%. B y contrast, saline was ineffective. High doses of the effective drugs that produced large disturbances in heart rate and/or acid-base equili brium were not considered in the pharmacological analysis, When a cons tant level of stimulation was used, different dose-dependent profiles of drug action were observed, Aspirin induced a slow and gradual depre ssion, although indomethacin, ketoprofen and paracetamol produced a pe ak effect within the first 10-min period and then reached a steady sta te phase for up to 30 min. The depressive effects of lysine clonixinat e appeared more stable. When recruitment curves were built with a rang e of nociceptive stimulus intensities, all the drugs produced a dose-d ependent decrease in the slopes and the areas under the recruitment cu rves without any major modification in the thresholds. The order of po tency was the same for both stimulation paradigms, e.g., aspirin < par acetamol < lysine clonixinate = ketoprofen < indomethacin. It is concl uded that NSAID elicit significant antinociceptive effects at a centra l level, which do not depend on the existence of a hyperalgesic or inf lammatory state.