BJA Advance Access originally published online on April 7, 2007
British Journal of Anaesthesia 2007 98(5):672-676; doi:10.1093/bja/aem075
Multicentre evaluation of the adenosine agonist GR79236X in patients with dental pain after third molar extraction
1 Anaesthesia Research Group, Peninsula Medical School, The John Bull Building, Tamar Science Park, Drake Circus, Plymouth PL6 8BU, UK
2 Department of Anaesthesia, Northwick Park Hospital, Watford Road, Harrow HA1 3UJ, UK
3 Department of Anaesthesia, The Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK
4 Department of Health Sciences and Division of Anaesthesia, Critical Care and Pain Management, University of Leicester, Leicester, UK
* Corresponding author. E-mail: robert.sneyd{at}pms.ac.uk
Background: Adenosine is analgesic in humans, and the selective adenosine A1 receptor agonist GR79236X has significant anti-nociceptive activity in an animal pain model of inflammatory pain.
Methods: Seventy-nine patients with moderate pain after third molar extraction under general anaesthesia were randomized to receive a 15 min double-blind infusion containing either GR79236X 4 µg kg –1, GR79236X 10 µg kg –1, diclofenac 50 mg, or saline placebo. Rescue analgesia was promptly available to all patients.
Results: Meaningful pain relief (mild or no pain) was attained by 9 (47%) patients in the placebo group, 12 (63%) patients in the GR79236 4 µg kg –1 group, 10 (48%) patients in the 10 µg kg –1 group, and 16 (80%) patients in the diclofenac 50 mg group. Neither dose of GR79236 produced a significant improvement over placebo, but diclofenac was superior to both placebo (P = 0.036) and GR79236 10 µg kg –1 (P = 0.034). Median times to rescue or additional analgesia were 62, 100, 60, and 363 min for patients receiving placebo, GR79236 4 µg kg –1, 10 µg kg –1, and diclofenac 50 mg, respectively (diclofenac significantly longer than placebo, P = 0.002 log-rank test). Pain control was poor in the placebo group and in both GR79236 groups, with between 79 and 86% of patients having good pain control (i.e. mild or no pain) for <20% of the time compared with only 30% of patients who received diclofenac.
Conclusion: We found no evidence of efficacy of GR79236 compared with placebo, but the active control diclofenac was effective. It is possible that a higher dose of GR79236 might have been effective or that i.v. administration of this drug does not achieve appropriate concentrations in the brain or peripheral nerves.
Keywords: acute pain, novel techniques; anaesthesia, dental; analgesics non-opioid, diclofenac; pain, acute