Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis.
OBJECTIVE
To describe an in vivo model in the rat in which change in weight distribution is used as a measure of disease progression and efficacy of acetaminophen and two nonsteroidal anti-inflammatory drugs (NSAIDs) in a model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA).


METHODS
Intra-articular injections of MIA and saline were administered to male Wistar rats (175-200 g) into the right and left knee joints, respectively. Changes in hind paw weight distribution between the right (osteoarthritic) and left (contralateral control) limbs were utilized as an index of joint discomfort. Acetaminophen and two archetypal, orally administered NSAIDs, naproxen and rofecoxib, were examined for their ability to decrease MIA-induced change in weight distribution.


RESULTS
A concentration-dependent increase in change in hind paw weight distribution was noted after intra-articular injection of MIA. Both naproxen and rofecoxib demonstrated the capacity to significantly (P<0.05) decrease hind paw weight distribution in a dose-dependent fashion, indicating that the change in weight distribution associated with MIA injection is susceptible to pharmacological intervention.


CONCLUSIONS
The determination of differences in hind paw weight distribution in the rat MIA model of OA is a technically straightforward, reproducible method that is predictive of the effects of anti-inflammatory and analgesic agents. This system may be useful for the discovery of novel pharmacologic agents in human OA.
Bove
S E
SE
Department of Inflammation Pharmacology, Pfizer Global Research and Development, Ann Arbor Laboratories, Ann Arbor, MI 48105, USA.
Calcaterra
S L
SL
Brooker
R M
RM
Huber
C M
CM
Guzman
R E
RE
Juneau
P L
PL
Schrier
D J
DJ
Kilgore
K S
KS
D000082:Acetaminophen / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000503:physiopathology; D007461:Iodoacetates; D008297:Male; D010003:Osteoarthritis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D016896:Treatment Outcome; D016474:Weight-Bearing
D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007461:Iodoacetates; D000082:Acetaminophen