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ODC-polyamine system is involved in morphine analgesia
S Genedani1, M Bernardi, S Tagliavini
1Institute of Pharmacology, University of Modena, Italy.
Abstract:
alpha-Difluoromethylornithine (DFMO) directly infused into a brain-lateral ventricle (12.5, 25 and 50 micrograms/rat) dose- and time-dependently inhibited brain ODC activity. While having no influence per se on pain threshold, DFMO significantly inhibited the analgesic activity of morphine (15 mg/kg i.p.), this effect being obtained when brain ODC activity was reduced by at least 80%. On the other hand, DFMO had no influence on number and affinity of brain opiate binding sites. Morphine per se neither modified whole brain ODC activity nor significantly affected the ODC inhibitory effect of DFMO. In more discrete brain areas (midbrain, brainstem) morphine actually increased ODC activity. The present results indicate that brain ODC/polyamines system may play a role in the analgesic activity of opioids, probably at a post-receptorial level or through a non-opiate receptor-linked mechanism.
Insights
Alpha-Difluoromethylornithine (DFMO) inhibits brain ornithine decarboxylase (ODC) activity and reduces morphine
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Ornithine decarboxylase (ODC) is a key enzyme in polyamine synthesis.
- Polyamines are essential for cell growth and differentiation.
- The role of brain ODC in opioid analgesia is not well understood.
Purpose of the Study:
- To investigate the effect of alpha-difluoromethylornithine (DFMO) on brain ODC activity.
- To determine the influence of DFMO on morphine-induced analgesia.
- To explore the involvement of the brain ODC/polyamines system in opioid analgesia.
Main Methods:
- Direct infusion of DFMO into the brain ventricles of rats.
- Measurement of brain ODC activity.
- Assessment of morphine's analgesic activity and opiate binding sites.
Main Results:
- DFMO dose-dependently inhibited brain ODC activity.
- DFMO significantly reduced morphine's analgesic effect when ODC activity was substantially inhibited.
- DFMO did not affect opiate receptor binding sites or morphine's effect on ODC inhibition.
- Morphine increased ODC activity in specific brain areas (midbrain, brainstem).
Conclusions:
- The brain ODC/polyamines system may play a role in opioid analgesia.
- This role might be mediated at a post-receptorial level or via a non-opiate receptor mechanism.
- Targeting the ODC/polyamines system could be a potential strategy for modulating pain perception.