Modification of morphine analgesia by venlafaxine in diabetic neuropathic pain model

Abstract

Abstract:Background: The purpose of this study was to investigate the influence of single or chronic (21 days) administration of the serotonin and noradrenaline reuptake inhibitor, venlafaxine, on the antinociceptive action of the opioid receptor agonist, morphine, in streptozotocin (STZ)-induced hyperalgesia. Methods:The studies were performed on male Wistar rats. Changes in nociceptive thresholds were determined using mechanical stimuli. Diabetes was induced by a single administration of STZ (40 mg/kg, im). Results: Venlafaxine was shown to modulate analgesic activity of morphine in STZ-induced hyperalgesia. However, whereas acute co-administration of venlafaxine increased the analgesic activity of morphine, chronic treatment with venlafaxine attenuated opioid efficacy. Conclusion: Depending on the mode of administration (single or long-term), venlafaxine modulates analgesic activity of morphine. Further investigations are necessary to clarify the mechanisms of these interactions, which may be clinically relevant.

Mechanisms of morphine–venlafaxine interactions in diabetic neuropathic pain model

“…In contrast, long-term treatment of VFX for 21 days decreased the antinociceptive action of MRF. Similar results were obtained in our previous study [8]. However, this effect was not associated with opioidergic or serotonergic system -neither naloxone nor the PCA changed pain thresholds after combined administration of VFX (21-days) and MRF.…”

“…Premedication with VFX (10 mg/kg, po) before MRF administration resulted in an increased antinociceptive effect of MRF, strong analgesic effect was observed through 60 min (R-S test) and 90 min (vF test) after injection (STZ + VFX-group, R-S test: À31.7 AE 2.1; À37. 8 (Fig. 1 A and B).…”

“…In our previous study we have reported that VFX modified analgesic effect of MRF depended on the mode of the administration (single or long-term) in streptozotocin (STZ)-induced neuropathy pain model [8]. However, the mechanisms of these interactions are still unknown.…”

Systemic synergism between codeine and morphine in three pain models in mice

“…Thus, the combinations that enhance opioid analgesic efficacy (e.g., synergism) include association with norepinephrine transport modulators, anti-inflammatory drugs, calcium channels a 2 -d ligands, local anesthetics, a 2 -adrenergic agonists, calcium channel blockers, cannabinoids, GABA B agonists, glial inhibitors, histamine and venlafaxine [4,21,27].…”

Ellagic acid enhances the antinociceptive action of venlafaxine in mouse acetic acid-induced pain: An isobolographic analysis

“…The observed synergy may be related to a pharmacokinetic or pharmacodynamic interaction that acts independently to block nociceptive processing; the latter seems more probable. Previous studies have demonstrated the synergistic interaction between VLF and several drug classes including k1-and k3-opioid receptor agonists, clonidine [14], and morphine [36]. However, additive interactions were observed when VLF was combined with tramadol [29], amlodipine and celecoxib [10].…”