Constitutive Cyclo-oxgenase-2 Is Involved in Central Nociceptive Processes in Humans

Background: Prostaglandins play a major role in inflammation and pain. They are synthesised by the two cyclooxygenase (COX) isoforms: COX-1, which is expressed constitutively in many cell types and COX-2, which is induced at the site of inflammation. However, unlike peripheral tissues, COX-2 is expressed constitutively in the central nervous system and may play a role in nociceptive processes. The present study aimed to investigate the role of constitutive COX-2 in the spinal transmission of nociceptive signals in humans. Methods: We used 12 healthy volunteers to compare the effects of the specific COX-2 inhibitor sodium parecoxib (1 mg/kg) or placebo, administered intravenously in a doubleblind and cross-over fashion, on the electrophysiological recordings of the nociceptive flexion (RIII) reflex. The RIII reflex is an objective psychophysiological index of the spinal transmission of nociceptive signals and was recorded from the biceps femoris after electrical stimulation of the sural nerve. Two experiments, seven days apart, were carried out on each volunteer. On each experimental day, the effects of parecoxib or placebo were tested on: 1) the RIII reflex threshold, 2) the stimulus-response curves of the reflex up to the tolerance threshold (frequency of stimulation: 0.1 Hz); 3) the progressive increase of the reflex and pain sensations (i.e. "wind-up" phenomenon) induced by a series of 15 stimulations at a frequency of 1 Hz (intensity 20% above RIII threshold). Results: Parecoxib, but not placebo, significantly reduced the slope of the stimulusresponse curve, suggesting a reduction in the gain of the spinal transmision of nociceptive signals. By contrast, the "wind-up" phenomenon was not significantly altered after administration of parecoxib or placebo. Conclusions: Our study shows that constitutive COX-2 modulates spinal nociceptive processes and that the anti-inflammatory and antinociceptive actions of COX-2 inhibitors are not necessarily related. in se rm -0 03 26 88 1, v er si on 1 6 O ct 2 00 8