Tonic versus phasic pain: dose-related effects of ketoprofen

Only recently has a new experimental technique been developed which combines tonic and phasic painful stimulation. By means of this technique the non-steroidal anti-inflammatory drug (NSAID) ibuprofen has been shown to produce a dose-related decrease in heterotopically applied phasic and tonic pain. The present study aimed to investigate the dose-related effects of the NSAID ketoprofen (50, 100, and 150 mg i.v.) when tonic and phasic stimuli were applied homotopically. Eighteen healthy volunteers participated in the double-blind, randomized, placebo-controlled study. After an initial training session subjects took part in four experiments, each of which was divided into three sessions (before, 30, and 120 min after drug administration). During each session 45 painful phasic CO2 stimuli of three concentrations were presented to the left nostril in randomized order (duration 200 ms; interval 40 s; 45%, 52%, and 59% v/v CO2). The left nostril was additionally stimulated with a constant stream of dry air, which produced a tonic painful sensation described as dull and burning. Subjects rated the intensity of the painful stimuli by means of visual analogue scales. Chemosomatosensory event-related potentials (CSSERPs) were recorded in response to phasic painful CO2 stimuli. Ketoprofen reduced the subjects' estimates of tonic pain in a dose-related manner. In contrast, given the special conditions of homotopic application of tonic and phasic painful stimuli, estimates of phasic pain increased significantly, corresponding to a significant increase in CSSERP amplitudes. An explanation of this inverse effect of the drug on responses to tonic and phasic pain may be a lateralized interaction between both C-fiber and A delta-fiber systems at a spinal or peripheral level.