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Modification of morphine analgesia by antidepressants in diabetic neuropathic pain model
Modification of morphine analgesia by antidepressants in diabetic neuropathic pain model Krystyna Cegielska-Perun1, Magdalena Bujalska-Zadro¿ny1, Ma³gorzata Dyba³a2, Agata Siwek2, Robert Wrzesieñ3, Helena E. Makulska-Nowak1 Department of Pharmacodynamics, Medical University of Warsaw, Krakowskie Przedmiecie 26/28, 00-927 Warsaw, Poland; Department of Cytobiology, Collegium Medicum, Jagiellonian University, Medyczna 9, 30-688 Kraków, Poland !Department of General and Experimental Pathology, Medical University of Warsaw, Krakowskie Przedmiecie 26/28, 00-927 Warsaw, Poland Introduction: Common side effects of non-treated or ill-treated diabetes lead to diabetic neuropathy. Fighting the neuropathic pain creates a great challenge for contemporary medicine as this kind of pain is resistant to opioidal analgesics. In order to neutralize the neuropathic pain different medications from various pharmaceutical groups are applied i.e. anticonvulsants, antidepressants, local anesthetics and other. Objectives: Assessing single and long term administration of antidepressants, with various working mechanisms on morphine analgesia, by streptozotocin -induced diabetes model in rats. Materials and Methods: The research has been conducted on a group of male Wistar rats weighting 250-350g. The model of researched diabetes was achieved by administering streptozotocin (40 mg/kg) in rats intramuscularly on the first day of the experiment. The pain threshold levels were determined by using mechanical stimuli (the Randall and Selitto test). Antinociceptive activity of morphine was assessed after one time and 21 day premedication of antidepressants. The results were later compared to the control group. The density of opioidal receptors of
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Pharmacological Reports, 2010, 62, suppl.
type mi was determined with the use of radioligand binding assay. Results: 1.After single and multi–dose administration of venlafaxine no significant changes in the density of opioidal receptors type mi have been found in the cerebral cortex in rats with established diabetes. 2. Antidepressants (venlafaxine, fluoxetine) depending on the dose amount, cause the weakening of hiperalgesia in streptozotocin-induced diabetes. 3. One single dose of venlafaxine and fluoxetine produces an intensified effect in morphine’s antinociceptive activity in the model of streptozotocin-induced diabetes. 4. Long term premedication of venlafaxine causes significant blockage of morphine’s antinociceptive activity; as for fluoxetine, it causes slight cancellation of morphine analgesia in the model of streptozotocininduced diabetes. Conclusions: The results of tests prove antidepressants from SNRI (Selective Serotonin and Noradrenaline Inhibitor) group (venlafaxine) more effective in neutralising diabetes neuropathy than those belonging to SSRI (Selective Serotonin Reuptake Inhibitor) group (fluoxetine).
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Pharmacological Reports, 2010, 62, suppl.
type mi was determined with the use of radioligand binding assay. Results: 1.After single and multi–dose administration of venlafaxine no significant changes in the density of opioidal receptors type mi have been found in the cerebral cortex in rats with established diabetes. 2. Antidepressants (venlafaxine, fluoxetine) depending on the dose amount, cause the weakening of hiperalgesia in streptozotocin-induced diabetes. 3. One single dose of venlafaxine and fluoxetine produces an intensified effect in morphine’s antinociceptive activity in the model of streptozotocin-induced diabetes. 4. Long term premedication of venlafaxine causes significant blockage of morphine’s antinociceptive activity; as for fluoxetine, it causes slight cancellation of morphine analgesia in the model of streptozotocininduced diabetes. Conclusions: The results of tests prove antidepressants from SNRI (Selective Serotonin and Noradrenaline Inhibitor) group (venlafaxine) more effective in neutralising diabetes neuropathy than those belonging to SSRI (Selective Serotonin Reuptake Inhibitor) group (fluoxetine).