Drug-induced side effects are frequently the limiting factor for achieving clinical analgesia. The purpose of this study was to provide a simple method for evaluating drug effects on both pain-specific and general motor activity in the same set of animals, thus allowing concomitant assessment of analgesic effects and side-effects. We also provide the outline for a computerized video analysis system which facilitates the analysis in terms of throughput and objectivity. The video analysis system is not commercially available, but some of the parameters may be obtained by other video tracking systems on the market.

Pain was induced in mice by subcutaneous injection of dilute formalin in a hind paw. Behavior was scored by using our video analysis system based on sequential digital image analysis. Orientation towards the injected paw was considered pain-specific behavior whereas locomotion, rearing and immobility was scored in order to quantify general behavior. In addition to inducing pain-specific behavior, formalin by itself reduced rearing and to a lesser extent locomotion and immobility. Morphine (3.1-25 mmol/kg) produced dose-related analgesia, increased locomotion and reduced immobility with slight separation between analgesic and motor effects. Higher doses caused a pronounced reduction in motor activity. Amphetamine in doses that had little effect on general behavior (0.78-3.1 mmol/kg) reduced the pain-related behavior while higher doses caused a marked motor activation. Diazepam (1.6-6.25 mmol/kg) reduced both pain-related and general behavior indiscriminately. The results are in agreement with the clinical experience that both morphine and amphetamine are analgesic compounds associated with side effects while diazepam has no direct analgesic properties.

We conclude that quantification of simple behaviors may predict some of the side effects of putative analgesics although the existence of species-specific drug-effects should be taken into account.