• Esther Berrocoso, Juan-Antonio Mico, Olivier Vitton, Philippe Ladure, Adrian Newman-Tancredi, Ronan Depoortère, and Laurent Bardin.
• Department of Neuroscience (Pharmacology and Psychiatry), Faculty of Medicine, University of Cadiz, 11003 Cadiz, Spain.
• Eur. J. Pharmacol. 2011 Mar 25;655(1-3):46-51.

AbstractMilnacipran, a serotonin/norepinephrine reuptake inhibitor (SNRI), has shown efficacy against several chronic pain conditions, including fibromyalgia. Here, we evaluated, in rats, its anti-allodynic effects following acute or sub-chronic treatment in a model of neuropathic pain (chronic constriction injury, CCI, of the sciatic nerve). Amitriptyline, a tricyclic antidepressant active pre-clinically and clinically against neuropathic pains, was added as a comparison compound. Upon acute i.p. administration, milnacipran was potently efficacious in the CCI model. It significantly reduced thermal allodynia in the cold (4°C) plate test (MED=2.5mg/kg), and attenuated mechanical allodynia in the von Frey filaments test (MED=10mg/kg). Given sub-chronically (7day, b.i.d.), milnacipran was effective at 10mg/kgi.p. in both tests. Acute amitriptyline (10mg/kgi.p.) was efficacious against mechanical, but less so against cold allodynia; under sub-chronic conditions, it was only active against mechanical allodynia. These data show that milnacipran is as efficacious as the reference compound amitriptyline in a pre-clinical model of injury-induced neuropathy, and demonstrate for the first time that it is active acutely and sub-chronically against cold allodynia. They also suggest that milnacipran has the potential to alleviate allodynia associated with nerve compression-induced neuropathic pain in the clinic (for example following discal hernia, avulsion or cancer-induced tissue damage).Copyright © 2011 Elsevier B.V. All rights reserved.

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