Morphine tolerance in arthritic rats and serotonergic system

To understand whether chronic inflammation alters the development of morphi ne tolerance, the tail-flick test was used to evaluate the analgesic effect of morphine (75 mg tablet, s.c.) in the arthritic rats at the day 9-12 aft er the inoculation with Freund's adjuvant. Spinal cord monoamines and amino acid neurotransmitters were concomitantly measured. Chronic inflammation a ttenuated the antinociceptive effect of morphine as tolerance developed fas ter in the arthritic rats compared to the vehicle-treated controls. In addi tion, ratio of 5-hydroxyindole-3-acetic acidi 5-hydroxytryptamine (5-HIAA/5 -HT) increased in the lumbar spinal cord of arthritic rats without any chan ge in the concentrations of norepinephrine, glutamate, aspartate or GABA. I nterestingly, increased serotonin turnover in the spinal cord was observed in both control and arthritic rats 24 hours after morphine treatment. Overa ll, the results suggest a significant role of serotonin up-regulation in th e spinal cord during chronic pain and the development of morphine tolerance . (C) 1999 Elsevier Science Inc.