Related Experiment Videos
Morphine tolerance in arthritic rats and serotonergic system
1Department of Anesthesiology, Chung-Gung Memorial Hospital, Tao-Yuan, Taiwan, ROC.
Abstract:
To understand whether chronic inflammation alters the development of morphine 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 after the inoculation with Freund's adjuvant. Spinal cord monoamines and amino acid neurotransmitters were concomitantly measured. Chronic inflammation attenuated the antinociceptive effect of morphine as tolerance developed faster in the arthritic rats compared to the vehicle-treated controls. In addition, ratio of 5-hydroxyindole-3-acetic acid/5-hydroxytryptamine (5-HIAA/5-HT) increased in the lumbar spinal cord of arthritic rats without any change in the concentrations of norepinephrine, glutamate, aspartate or GABA. Interestingly, increased serotonin turnover in the spinal cord was observed in both control and arthritic rats 24 hours after morphine treatment. Overall, the results suggest a significant role of serotonin up-regulation in the spinal cord during chronic pain and the development of morphine tolerance.
Insights
Chronic inflammation accelerates morphine tolerance development in rats. This involves increased serotonin turnover in the spinal cord, suggesting a role for serotonin in pain and tolerance.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Opioid analgesics like morphine are crucial for pain management.
- Developing tolerance to morphine limits its long-term effectiveness.
- Chronic inflammation is a common condition associated with persistent pain.
Purpose of the Study:
- To investigate the impact of chronic inflammation on the development of morphine tolerance.
- To explore the neurochemical changes in the spinal cord associated with inflammation and morphine tolerance.
Main Methods:
- Utilized the tail-flick test to assess morphine's analgesic effect in arthritic rats.
- Measured spinal cord monoamines and amino acid neurotransmitters.
- Compared tolerance development in arthritic rats versus vehicle-treated controls.
Main Results:
- Chronic inflammation significantly attenuated morphine's antinociceptive effect, leading to faster tolerance development.
- Arthritic rats showed an increased ratio of 5-hydroxyindole-3-acetic acid/5-hydroxytryptamine (5-HIAA/5-HT) in the lumbar spinal cord.
- No significant changes in norepinephrine, glutamate, aspartate, or GABA concentrations were observed.
- Morphine treatment increased serotonin turnover in the spinal cord of both control and arthritic rats.
Conclusions:
- Chronic inflammation accelerates the development of morphine tolerance.
- Increased serotonin turnover in the spinal cord plays a significant role in chronic pain and morphine tolerance.
- Serotonin up-regulation is a key mechanism underlying morphine tolerance in the context of chronic inflammation.