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Constitutive cyclooxygenase-2 is involved in central nociceptive processes in humans.
Martin F., Fletcher D., Chauvin M., Bouhassira D.
Anesthesiology / Anaesthesiology 106, 5 (2007) 1013-8 - http://www.hal.inserm.fr/inserm-00326881
(17457134)
Constitutive cyclooxygenase-2 is involved in central nociceptive processes in humans.
Frédéric Martin1, Dominique Fletcher1, 2, Marcel Chauvin1, 2, Didier Bouhassira () 1
1 :  Physiopathologie et Pharmacologie Clinique de la Douleur
INSERM : U792 – Université de Versailles Saint-Quentin-en-Yvelines
Hopital Ambroise Pare 9, Avenue Charles de Gaulle 92100 BOULOGNE BILLANCOURT
France
2 :  Service d'anesthésie
Assistance publique - Hôpitaux de Paris (AP-HP) – Hôpital Raymond Poincaré
92380 Garches
France
COX-2 inhibitors and analgesia
BACKGROUND: Prostaglandins play a major role in inflammation and pain. They are synthesized 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 current study aimed to investigate the role of constitutive COX-2 in the spinal transmission of nociceptive signals in humans. METHODS: The authors 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 double-blind and crossover fashion, on the electrophysiologic recordings of the nociceptive flexion (RIII) reflex. The RIII reflex is an objective psychophysiologic index of the spinal transmission of nociceptive signals and was recorded from the biceps femoris after electrical stimulation of the sural nerve. Two experiments, 7 days apart, were conducted in 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), and (3) the progressive increase of the reflex and pain sensations (i.e., "windup" 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 stimulus-response curve, suggesting a reduction in the gain of the spinal transmission of nociceptive signals. By contrast, the windup phenomenon was not significantly altered after administration of parecoxib or placebo. CONCLUSIONS: This study shows that constitutive COX-2 modulates spinal nociceptive processes and that the antiinflammatory and antinociceptive actions of COX-2 inhibitors are not necessarily related.
Sciences du Vivant/Médecine humaine et pathologie/Physiologie
Anglais
0003-3022

Articles dans des revues avec comité de lecture
10.1097/01.anes.0000265162.39932.33
Anesthesiology / Anaesthesiology
internationale
05/2007
106
5
1013-8

Adult – Cross-Over Studies – Cyclooxygenase 2 – Double-Blind Method – Female – Humans – Isoxazoles – Male – Pain – Pain Threshold – Reflex – Spinal Cord
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