Effects of long term polyarthritis and subsequent NSAID treatment on activity with disassociation of tactile allodynia in the mouse

Chronic pain has profound effects on activity. Previous reports indicate chronic inflammatory conditions result in reduced activity, which normalizes upon pain treatment. However, there is little systematic investigation of this process. Rheumatoid arthritis is an autoimmune disorder that causes significant joint pain. The K/BxN serum transfer mouse has been characterized as a model for rheumatoid arthritis and chronic pain. We investigated the activity of mice following K/BxN serum transfer vs. control serum and observed the activity changes following delivery of an NSAID, ketorolac. Previous studies have used running wheels and laser beams to monitor activity; we chose to validate a model using cost-effective infrared sensors on individual cages. Each mouse had its baseline activity obtained, which showed significant variation between individual C57Bl/6 mice. Arthritic mice had significantly decreased activity for only the first 11 nights. Conversely, previous work has shown that these animals display tactile allodynia that persists for at least 45 days. Mice were treated with ketorolac in their drinking water (10 mg/kg, 15 mg/kg, or 20 mg/kg) for nights 6-8. The two highest doses showed significant normalization of activity levels. Four nights after ketorolac was stopped, treated animals were still significantly more active than control. The reversal of the reduced activity provides support that the depression relates to the arthritic pain state of the animal. These results indicate the efficacy of activity monitoring to better investigate behavior in persistent pain states. However, insofar as depressed activity reflects pain and disability, the present work raises questions as to the relevance of the tactile thresholds in defining behaviorally relevant pain states.