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.

The sunburn pain model: the stability of primary and secondary hyperalgesia over 10 hours in a crossover setting.

UNLABELLED: It was our aim to study the within-day stability and between-day repeatability of ultraviolet B (UVB) light-induced primary and secondary hyperalgesia over 10 h. Twenty hours after UVB irradiation of a skin spot (r = 2.5 cm) on the upper leg of 8 healthy volunteers the areas of secondary hyperalgesia to pinprick and pain tolerance thresholds to heat (HPTT) and electrical stimuli (5 and 250 Hz, electrical pain tolerance thresholds [EPTT]) were assessed. Measurements were repeated for 10 h at 2-h intervals and in 2 different sessions. Large areas of secondary hyperalgesia to pin prick were observed (5995 mm(2); SD, 1645). Primary hyperalgesia was evidenced by significant decreases of HPTT (mean difference, 6.5 degrees C; 95% confidence interval, 6.1-6.8; P < 0.001) and EPTT at 250 Hz (mean difference, 0.45 mA; 95% confidence interval, 0.13-0.78; P < 0.05) compared to normal skin. There was no trend within one session of either primary (P = 0.14 for HPTT) or secondary hyperalgesia (P = 0.95) and no difference between the two sessions (primary hyperalgesia, P = 0.28; secondary hyperalgesia, P = 0.07). The sunburn pain model provides a long time course of stable hyperalgesia with a high within-day stability and between-day repeatability for primary and secondary hyperalgesia. IMPLICATIONS: The sunburn pain model provides a long time course of stable hyperalgesia with a high within-day stability and between-day repeatability for primary and secondary hyperalgesia.