PT  - JOURNAL ARTICLE
AU  - David J. Matson
AU  - Daniel C. Broom
AU  - Susan R. Carson
AU  - James Baldassari
AU  - John Kehne
AU  - Daniel N. Cortright
TI  - Inflammation-Induced Reduction of Spontaneous Activity by Adjuvant: A Novel Model to Study the Effect of Analgesics in Rats
AID  - 10.1124/jpet.106.109736
DP  - 2007 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 194--201
VI  - 320
IP  - 1
4099  - http://jpet.aspetjournals.org/content/320/1/194.short
4100  - http://jpet.aspetjournals.org/content/320/1/194.full
SO  - J Pharmacol Exp Ther2007 Jan 01; 320
AB  - The majority of rodent models used to evaluate analgesic drug effects rely on evoked measures of nociceptive thresholds as primary outcomes. These approaches are often time-consuming, requiring extensive habituation sessions and repeated presentations of eliciting stimuli, and are prone to false-positive outcomes due to sedation or tester subjectivity. Here, we describe the reduction of spontaneous activity by adjuvant (RSAA) model as an objective and quantifiable behavioral model of inflammatory pain that can predict the analgesic activity of a variety of agents following single-dose administration. In the RSAA model, activity was measured in nonhabituated rats using standard, photocell-based monitors. Bilateral inflammation of the knee joints by complete Freund's adjuvant (CFA) reduced the normal level of activity (horizontal locomotion and vertical rearing) by ∼60% in a novel environment. This reduction in activity was dose-dependently reversed by ibuprofen, rofecoxib, celecoxib, piroxicam, and dexamethasone, whereas gabapentin and amitriptyline were inactive. Morphine significantly reversed the activity-suppressing effects of CFA, at 1 mg/kg s.c., but at higher doses locomotor activity progressively declined, coincident with the induction of sedation. In contrast to morphine and anti-inflammatory therapies, amphetamine did not affect vertical rearing, even though it increased horizontal locomotion. Thus, unlike standard measures of analgesia such as alteration in thermal or mechanical sensitivity, the RSAA model operationally defines analgesia as a drug-induced increase in spontaneous behavior (vertical rearing in a novel environment). We conclude that the RSAA model is valuable as an objective measure of analgesic efficacy that is not dependent on an evoked stimulus response. The American Society for Pharmacology and Experimental Therapeutics