Upside assay sensitivity in a dental pain model

The extent of surgical trauma was related to postoperative pain intensity in a previous study. However, more extensive surgical procedures with higher baseline pain intensity did not appear to influence the ability to document the additive analgesic effect of codeine when given with paracetamol, partly due to large interindividual variation in baseline pain intensity. The aim of the present study was to attempt to improve upside assay sensitivity in this dental pain model by: (1) selecting patients with high baseline pain intensity; and (2) closer supervision of outpatients' drug intake and compliance with protocol. Only patients with baseline pain greater than or equal to 50 on a 100 mm visual analogue scale after wisdom tooth surgery were included. Twenty patients were given paracetamol 1000 mg with or without codeine 60 mg in repeated doses in a randomized and double-blind manner. Intake of the first dose of test medication and its effects were closely supervised, while the two following doses were taken at 3-h intervals after the patient had left the clinic. Pain intensity was measured with the visual analogue scale for 8 h. More pain relief was revealed when codeine 60 mg was added to paracetamol 1000 mg on the following measures of effect: change of pain intensity with time (p<0.05, Mann-Whitney), sum of pain intensities (p = 0.019), pain intensity difference (p less than or equal to 0.05), sum of pain intensity differences (p < 0.05), pain reduction index (p < 0.05) and global-evaluation score (p = 0.006). The study confirms that this dental pain model, when controlled for sufficient and homogeneous baseline pain and patient compliance, does have sufficient upside assay sensitivity to discriminate between paracetamol with and without codeine.