Mechanisms of morphine-venlafaxine interactions in diabetic neuropathic pain model

作者：Cegielska Perun Krystyna^*; Tatarkiewicz Jan; Siwek Agata; Dybala Malgorzata; Bujalska Zadrozny Magdalena

来源：Pharmacological Reports, 2015, 67(1): 90-96.

DOI：10.1016/j.pharep.2014.08.008

• Diabetes
• Morphine
• Venlafaxine
• Interactions
• Yohimbine

Background: we investigated the possible mechanisms involved in the interactions of venlafaxine (VFX), a selective serotonin and noradrenaline reuptake inhibitor, and morphine (MRF), an opioid receptor agonist, after acute and chronic VFX treatment in diabetic neuropathic pain model (DNPM).
Methods: The studies were performed on male rats. The changes in nociceptive thresholds were determined by using mechanical stimuli (the Randall-Selitto and the von Frey tests). Diabetes was induced by intramuscular administration of streptozotocin. In order to investigate the mechanism of interaction, animals were also pretreated with naloxone (NLX), a nonselective opioid antagonist, yohimbine (YOH), a nonselective alpha(2)-adrenergic antagonist, and p-chloroamphetamine (PCA), a neurotoxin that destroys serotonergic neurons. The mu-opioid receptors' density was determined with the use of radioligand binding assay.
Results: VFX potentiated antinociceptive action of MRF after acute administration of VFX and this effect was decreased by pretreatment of NLX, YOH and PCA. On the contrary, VFX administered for 21 days prior to MRF significantly decreased the analgesic action of MRF; this effect was augmented only after YOU pretreatment. Also, 21-days administration of VFX caused decreasing tendency in the number of mu-opioid receptors in the brain stem.
Conclusions: The results of our study show that single administration of VFX potentiates antinociceptive action of morphine in DNPM. This effect is probably mediated by both, noradrenergic and serotonergic systems. On the other hand, 21-days administration of VFX significantly decreases analgesic action of MRF. Moreover, there is a possibility that VFX acts as an antagonist of N-methyl-D-aspartate receptors.

• 出版日期2015-2