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

Arthritis Rheum. 2005 Nov;52(11):3470-8. doi: 10.1002/art.21403.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / therapeutic use
  • Activity Cycles / drug effects
  • Activity Cycles / physiology*
  • Analgesics / therapeutic use
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / physiopathology*
  • Arthritis, Experimental / psychology
  • Behavior, Animal*
  • Chronic Disease
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods*
  • Hyperalgesia / physiopathology
  • Hyperalgesia / psychology
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Pain / drug therapy
  • Pain / physiopathology*
  • Pain / psychology
  • Pain Measurement
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Acetaminophen