title: Circadian pattern of spontaneous behavior in monarthritic rats: a novel global approach to evaluation of chronic pain and treatment effectiveness.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Faculty of Medicine, Medical Laboratory of Pharmacology, 63001 Clermont-Ferrand Cedex 1, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Millecamps
authors.forename: Didier
authors.initials: D
authors.lastname: Jourdan
authors.forename: Sabine
authors.initials: S
authors.lastname: Leger
authors.forename: Monique
authors.initials: M
authors.lastname: Etienne
authors.forename: Alain
authors.initials: A
authors.lastname: Eschalier
authors.forename: Denis
authors.initials: D
authors.lastname: Ardid
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use; D000204:Activity Cycles / Q000187:drug effects / Q000502:physiology*; D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D001522:Behavior, Animal; D002908:Chronic Disease; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006930:Hyperalgesia / Q000503:physiopathology / Q000523:psychology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen