Effect of long-term ketamine administration on vocalization to paw pressure and on spinal wind-up activity in monoarthritic rats

The antinociceptive effect of long-lasting ketamine administration (mini-osmotic pump) was studied in monoarthritic rats by using hindpaw pressure testing and wind-up measurement in a C-fiber reflex paradigm. Chronic ketamine induced antinociception in the monoarthritic paw and significantly suppressed mechanical hyperalgesia during the 14-day treatment period. The treatment also reduced C-reflex wind-up in the monoarthritic hindpaw. After pump removal, vocalization thresholds and spinal wind-up scores from the monoarthritic paw returned to control values, while hyperalgesia developed in the normal paw. Results suggest that ketamine upregulates NMDA receptors upon long-term administration, resulting in hyperalgesic response in the normal paw after drug withdrawal.