Rofecoxib attenuates both primary and secondary inflammatory hyperalgesia: a randomized, double blinded, placebo controlled crossover trial in the UV-B pain model.
The analysis of drug's influence on peripheral and central sensitisation can give useful information about its mode of action and can lead to more efficacy in the treatment of pain. Peripheral inflammation is associated with peripheral expression and up-regulation of cyclooxygenase 2 (COX-2) in the CNS. The relative contribution of COX-2 mediated central sensitisation may be prominent under inflammatory conditions. In this randomized, double blinded, placebo controlled cross-over trial the effects of multidoses of the COX-2 selective inhibitor rofecoxib on primary and secondary hyperalgesia were evaluated in the UVB pain model. Twenty-four hours after local UVB irradiation at the upper leg of 42 healthy volunteers heat pain perception (HPPT) and heat pain tolerance thresholds (HPTT) were assessed within the inflammation. The area of secondary hyperalgesia was determined by pin prick test. Subjects received oral rofecoxib 50, 250, 500 mg or placebo. Pain testing was repeated after 3 and 6 h. Compared to placebo, rofecoxib significantly increased HPPT (1.55 and 1.08 degrees C, P<0.0001 and P=0.0333), HPTT (1.74 and 1.58 degrees C, P<0.0001 and P<0.0001), and reduced the mean area of secondary hyperalgesia by 15.6% (P=0.007) and 16.8% (P<0.001) after 3 and 6 h. No significant difference between the three dosage groups was observed. These data confirm peripheral effects of rofecoxib in a human inflammatory UV-B pain model and provide circumstantial evidence that even a standard clinical dose of rofecoxib reduces central hyperalgesia in inflammatory pain. We confirm that the effect of single oral dose of rofecoxib plateaus at 50 mg.
Sycha
Thomas
T
Department of Neurology, Medical University of Vienna, Währinger-Gürtel 18-20 A-1090 Vienna, Austria Department of Anesthesia and General Intensive Care Medicine, Medical University of Vienna, Vienna, Austria Department of Clinical Pharmacology, Medical University of Vienna,Vienna, Austria Institute for Medical Computersciences, Medical University of Vienna, Vienna, Austria GlaxoSmithKline, Addenbrooke's Centre for Clinical Investigation, Cambridge, UK.
Anzenhofer
Sebastian
S
Lehr
Stephan
S
Schmetterer
Leopold
L
Chizh
Boris
B
Eichler
Hans-Georg
HG
Gustorff
Burkhard
B
D000328:Adult; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007249:Inflammation / Q000150:complications; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010919:Placebos; D012039:Regional Blood Flow / Q000502:physiology; D012867:Skin / Q000098:blood supply; D013450:Sulfones / Q000627:therapeutic use*; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects*
D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D010919:Placebos; D013450:Sulfones; C116926:rofecoxib