Variation in surgical trauma and baseline pain intensity: effects on assay sensitivity of an analgesic trial

The aims of this study were to test the hypotheses that the type of 3rd molar removal determines baseline pain and that baseline pain influences analgesic assay sensitivity. Three groups of patients were studied: (i) 100 patients that had one fully erupted maxillary 3rd molar extracted; (ii) 95 patients that had one lower impacted 3rd molar surgically removed; and (iii) 98 patients that had two ipsilateral impacted 3rd molars surgically removed. In a randomized, double-blind fashion, the patients received (every third hour, three times) either: (i) paracetamol 1g; (ii) paracetamol 1g plus codeine 60 mg; or (iii) placebo. Baseline pain intensity (100 mm Visual Analogue Scale) was significantly lower after extraction (8 mm (2-20)) (=median (25th -75th percentile) than after surgical removal of one 3rd molar (35 mm (15-57)), which was significantly lower than pain intensity after surgical removal of two 3rd molars (49 mm (24-82)). Analgesic effects of the active test drugs were superior to placebo. Paracetamol with and without codeine could be distinguished in patients after surgical removal of one 3rd molar. In conclusion, baseline pain was related to the degree of surgical trauma, but large inter-individual variation in baseline pain intensity reduced the ability to distinguish between paracetamol with and without codeine.