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Aims To determine the comparative efficacy of a new novel adenosine agonist (WAG 994) in postoperative pain after third molar surgery. Methods One hundred and twenty-two patients with postoperative pain after third molar surgery were randomised in a placebo double-blind trial with an active control group. In the early postoperative period patients received either a single dose of WAG 994 1 mg, ibuprofen 400 mg or matched placebos. Pain intensity score was recorded on serial visual analogue scales over a 6 h investigation period. Similarly, pain relief was completed on a 4 point categorical scale at each evaluation point. Patients had access to escape analgesic and if these were taken, the time and dosage were recorded. A sparse sampling technique was used to investigate the relationship between analgesic effects and plasma concentrations of WAG 994. Results All three treatment groups were matched for various demographic variables. For all efficacy measures, WAG 994 was not significantly different from placebo (P >0.05), whereas ibuprofen 400 mg was significantly superior to placebo (P

1. The effects of aspirin 1000 mg, paracetamol 1000 mg, codeine 60 mg on somatosensory evoked potentials (SEPs) were measured in a four-way cross-over study. 2. SEPs were elicited by electrical stimulation of the skin overlying the digital nerve at intensities close to pain threshold. 3. Amplitudes and latencies of both early and late SEPs were recorded, as well as first sensory threshold and subjective pain threshold. 4. None of the study medications affected the amplitude or latency of the late SEP components (100-250 ms post-stimulus). The amplitude of early components (15-30 ms post-stimulus) was also unaffected, but aspirin shortened the latency 30 min after ingestion. 5. Sensory detection and pain threshold to electrical skin stimulation were also unaffected by any of the study medications despite subjective central effects with codeine.

1. Recent evidence has hinted at a peripheral site of action of morphine analgesic efficacy. 2. Previous studies by the same authors have developed a model for testing local analgesic efficacy by placing drugs into tooth sockets after third molar surgery. 3. The present studies test the hypothesis of local morphine activity at two dosage concentrations, 100 ng ml-1 and 100 micrograms ml-1 after third molar surgery. 4. No significant analgesic efficacy was found at either dose when compared with placebo.

1. Single doses (500 and 1000 mg) of both buffered aspirin and aspirin tablets were compared with placebo in a randomised double-blind trial of parallel design in patients with postoperative pain after third molar surgery. 2. Only buffered aspirin 500 mg provided significant pain relief (P = 0.016) during the 5 h investigation period. 3. A significant correlation (P = 0.004) was observed between overall pain scores after the various aspirin treatments and aspirin esterase activity. 4. Buffered aspirin preparations afforded a slight advantage over aspirin tablets in the control of postoperative pain after third molar surgery. However, the duration of analgesia was short (approximately 2 h). 5. Aspirin esterase activity appears to be an important determinant of the drug's efficacy in postoperative dental pain.

1. Benorylate (4-acetamido phenyl-O-acetylsalicylate) hydrolysis in vitro by human plasma and by human liver microsomes and cytosol has been investigated. 2. Benorylate was hydrolysed by a route involving initial hydrolysis of the acetyl group to yield phenetsal followed by hydrolysis to paracetamol and salicylate. Hydrolysis via acetylsalicylate was minor. 3. Benorylate was more actively hydrolysed by liver cytosol than microsomes and about 10 times faster than plasma. 4. Following a single oral dose benorylate (4 g) to volunteers only salicylate and paracetamol were detected in the plasma. 5. The therapeutic effects of benorylate appear to be mediated by salicylate and paracetamol.

Aspirin 1200 mg was compared with placebo in a randomised, double-blind, crossover study in 15 patients with postoperative pain after removal of impacted lower third molars. Over a 5 h investigation period, patients reported significantly less pain (P less than 0.01) after treatment with aspirin, than after treatment with placebo. Peak concentrations of aspirin occurred at 15 min after dosage. Significant negative correlations were observed between plasma aspirin esterase activity and both AUC aspirin (r = -0.904, P less than 0.001) and AUC analgesia (r = -0.91, P less than 0.001). Similarly, a significant correlation was observed between AUC aspirin and AUC analgesia (r = 0.96, P less than 0.001). Evidence from this study would suggest that an individual's pain relief in postoperative dental pain is determined by the rate of aspirin hydrolysis to salicylate.