Circadian pattern of spontaneous behavior in monarthritic rats: a novel global approach to evaluation of chronic pain and treatment effectiveness.
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.
Millecamps
Magali
M
Faculty of Medicine, Medical Laboratory of Pharmacology, 63001 Clermont-Ferrand Cedex 1, France.
Jourdan
Didier
D
Leger
Sabine
S
Etienne
Monique
M
Eschalier
Alain
A
Ardid
Denis
D
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
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen