Circadian pattern of spontaneous behavior in monarthritic rats: A novel global approach to evaluation of chronic pain and treatment effectiveness

  • Millecamps M
  • Jourdan D
  • Leger S
 et al. 
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Abstract

Objective
Preclinical evaluation is an essential step in the assessment of new antiinflammatory or analgesic drugs. This study was undertaken to develop a new mode of evaluation of drug effectiveness based on behavior indicating well-being in a rat model of chronic inflammatory pain. We chose to examine the circadian pattern of spontaneous behavior.
Methods
The work was performed with a model of chronic monarthritis induced by Freund's complete adjuvant. Variations in behavioral patterns during the time course of arthritis were analyzed. In a second phase, the impact of acetaminophen and 2 nonsteroidal antiinflammatory drugs (aspirin and celecoxib), which are currently used in clinical practice to treat chronic inflammation, was studied after 7 days of treatment.
Results
The nocturnal pattern of activity of healthy rats comprised 3 main bursts. Chronic painful monarthritis altered this spontaneous pattern of nocturnal behavior (normal period of activity). Monarthritic rats showed a decrease in the total time spent in activity during the night, and lost their pattern of activity. These behavioral disturbances were reversed after long-term treatment with acetaminophen or celecoxib, with celecoxib appearing to be more effective. Aspirin was ineffective.
Conclusion
These results enabled us to test this new procedure as a means of assessing well-being or ill- being during stages of chronic inflammatory pain in rats, and the effectiveness of repeated pharmacologic treatments.

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