Milnacipran attenuates hyperalgesia and potentiates antihyperalgesic effect of tramadol in rats with mononeuropathic pain

Önal, Aytül; Parlar, Aytül; Ülker, Sibel

doi:10.1016/j.pbb.2007.08.001

Cited by 32 publications

(20 citation statements)

References 46 publications

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“…Our results are consistent with a previous finding where the selective serotonin reuptake inhibitor (SSRI), fluoxetine, enhanced antinociceptive and antiallodynic effects of morphine in diabetic and sciatic-nerve-ligated mice [24]. Other reports also revealed that acute co-administration of serotonin and noradrenaline reuptake inhibitors (milnacipram and venlafaxine) and a tricyclic antidepressant (doxepin) with tramadol potentiated the antihyperalgesic effect of tramadol in the CCI model of neuropathic pain [17,26,28].…”

supporting

confidence: 93%

Modification of morphine analgesia by venlafaxine in diabetic neuropathic pain model

Cegielska-Perun

Bujalska‐Zadrożny

Makulska-Nowak

2012

Pharmacological Reports

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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.

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supporting

confidence: 93%

Modification of morphine analgesia by venlafaxine in diabetic neuropathic pain model

Cegielska-Perun

Bujalska‐Zadrożny

Makulska-Nowak

2012

Pharmacological Reports

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“…Antagonizing spinal monoamine receptors can block the antinociceptive effects of milnacipran, and the noradrenergic system in particular appears important to these effects (Onal et al, 2007;Obata et al, 2010;Nakajima et al, 2012). In the present studies, whereas blocking spinal a 2 -adrenoceptors with atipamezole reversed the effects of milnacipran in naïve animals and the early phase of the model, this was not so in the late phase.…”

Section: Discussioncontrasting

confidence: 48%

The Antinociceptive Effect of Milnacipran in the Monosodium Iodoacetate Model of Osteoarthritis Pain and Its Relation to Changes in Descending Inhibition

Burnham

Dickenson

2013

J Pharmacol Exp Ther

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Osteoarthritis (OA) is a chronic joint disorder whose principal symptom is chronic pain. Current analgesics are inadequate and the mechanisms contributing to this pain are poorly understood but likely to include both local joint changes and central consequences. These studies used monoamine receptor agents combined with behavioral studies and single-unit dorsal horn recordings to examine whether descending noradrenergic and serotonergic inhibitions are altered in the monosodium iodoacetate model of OA pain, and whether increasing these inhibitions with the serotonin/noradrenaline reuptake inhibitor milnacipran can attenuate the attendant hypersensitivity. Early and late in the course of this model, milnacipran (s.c.) reduced behavioral hypersensitivity, and inhibited evoked responses from sensitized dorsal horn neurons. In naïve animals and the early, but not late, phase of the model, spinal administration of the a 2 -adrenoceptor antagonist atipamezole fully reversed this neuronal inhibition, whereas atipamezole administered alone revealed that endogenous noradrenergic inhibition was reduced in the late phase. Blocking spinal 5-hydroxytryptamine-7 receptors with (2R)-1-[(3-hydroxyphenyl) sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride suggested that the effects of milnacipran in the late phase were partly mediated by these receptors, and that descending serotonergic inhibition was increased in this phase. An opioidergic mechanism behind the effects of milnacipran was indicated by a partial reversal of these effects with naloxone. These studies demonstrate antinociceptive effects for milnacipran in a model of OA pain, whose effects come via descending serotonergic and noradrenergic, as well as opioidergic, pathways. Variations in the activity of these pathways over the course of this model may contribute to the presence of behavioral hypersensitivity and determine through which endogenous systems milnacipran exerts its effects.

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“…The present study further demonstrated a significant attenuation of paclitaxel-induced mechanical allodynia by repeated milnacipran or fluvoxamine treatment. Milnacipran and fluvoxamine are used for the treatment of acute and neuropathic pain as a supplementary analgesic (16,21). There have been several reports indicating that milnacipran and fluvoxamine have significant antinociceptive effects against nociceptive and inflammatory pain (20,22,27,28,30).…”

Section: Discussionmentioning

confidence: 99%

“…Yokogawa et al demonstrated that milnacipran significantly attenuated late phase paw licking behavior in the formalin test (30) and also reversed mechanical allodynia in the chronic constriction injury model or spinal nerve ligation model of neuropathic pain (9,28). In addition, milnacipran had an antiallodynic effect on the streptozotocin-induced diabetic neuropathy model (9) and potentiated the antihyperalgesic effect of tramadol (opioid analgesic) (21). However, the antiallodynic effects of milnacipran and fluvoxamine on paclitaxel-induced mechanical allodynia remain unknown.…”

Section: Time Course and Dose-response Of Paclitaxel-induced Mechanicmentioning

confidence: 99%

Effects of repeated milnacipran and fluvoxamine treatment on mechanical allodynia in a mouse paclitaxel-induced neuropathic pain model

et al. 2013

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Paclitaxel is widely used in cancer chemotherapy for the treatment of solid tumors, but it frequently causes peripheral neuropathy. Milnacipran, a serotonin/noradrenaline reuptake inhibitor and fluvoxamine, a selective serotonin reuptake inhibitor, have shown efficacy against several chronic pain syndromes. In this study, we investigated the attenuation of paclitaxel-induced mechanical allodynia in mice by milnacipran and fluvoxamine. Paclitaxel was administered once per day (2 mg/kg, intraperitoneally (i.p.)) for 5 days to mice. Mechanical allodynia was evaluated by measuring the withdrawal response to stimulation with a von Frey filament. In paclitaxel-treated mice, mechanical allodynia was observed on days 3-15 of paclitaxel administration. A single administration of milnacipran (20 mg/kg, i.p.) or fluvoxamine (40 mg/kg, i.p.) had no effect on paclitaxel-induced mechanical allodynia. However, repeated administration of milnacipran (10, 20 mg/kg, once per day, i.p.) for 5 days significantly reduced paclitaxel-induced mechanical allodynia. In contrast, repeated fluvoxamine administration (40 mg/kg, once per day, i.p.) for 5 days resulted in a weak attenuation of paclitaxel-induced mechanical allodynia. These results suggest that chronic paclitaxel administration induces mechanical allodynia, and that repeated milnacipran administration may be an effective therapeutic approach for the treatment of neuropathic pain caused by paclitaxel treatment for cancer.Peripheral neurotoxicity induced by antineoplastic drugs (taxanes, vinca-alkaloids and platin-based compounds) is a clinically significant complication that can be dose-limiting and can substantially diminish quality of life. Paclitaxel is commonly used for the treatment of solid tumors and ovarian and breast cancers. Paclitaxel induces antimitotic actions by impeding the cell cycle in the late phases of mitosis, stabilizing microtubule formation, and ultimately inducing apoptosis (26). However, paclitaxelinduced peripheral neuropathy is a side-effect of chemotherapeutic treatment which often manifests as bilateral pain in the extremities in a stocking and glove-type distribution (6), sometimes greatly impairing the patients' quality of life and their ability to perform normal activities of daily living. To date, therapeutic drugs have been evaluated using various animal models of paclitaxel-induced allodynia. Ethosuximide (7), gabapentin (14), thalidomide and minocycline (3), neurotropin (11) and acetyl-L-carnitine (8) have been examined against the paclitaxelinduced neuropathic pain model, although studies regarding their efficacy have not been conclusive. Supplementary analgesics (antidepressants and anticonvulsants) have suppressive effects on opioid-resistant neuropathic pain (16,24), and antidepressants are widely used for the treatment of neuropathic pain. Antidepressants, especially tricyclic antidepressants (TCAs), are regarded as first-line drugs for the treatment of neuropathic pain (16). Recently, more selective monoamine reuptake inhibitors...

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Milnacipran attenuates hyperalgesia and potentiates antihyperalgesic effect of tramadol in rats with mononeuropathic pain

Cited by 32 publications

References 46 publications

Modification of morphine analgesia by venlafaxine in diabetic neuropathic pain model

Modification of morphine analgesia by venlafaxine in diabetic neuropathic pain model

The Antinociceptive Effect of Milnacipran in the Monosodium Iodoacetate Model of Osteoarthritis Pain and Its Relation to Changes in Descending Inhibition

Effects of repeated milnacipran and fluvoxamine treatment on mechanical allodynia in a mouse paclitaxel-induced neuropathic pain model

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