title: Evaluation of milnacipran, in comparison with amitriptyline, on cold and mechanical allodynia in a rat model of neuropathic pain.
abstract: Milnacipran, 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).
authors.affiliation: Department of Neuroscience (Pharmacology and Psychiatry), Faculty of Medicine, University of Cadiz, 11003 Cadiz, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Berrocoso
authors.forename: Juan-Antonio
authors.initials: JA
authors.lastname: Mico
authors.forename: Olivier
authors.initials: O
authors.lastname: Vitton
authors.forename: Philippe
authors.initials: P
authors.lastname: Ladure
authors.forename: Adrian
authors.initials: A
authors.lastname: Newman-Tancredi
authors.forename: Ronan
authors.initials: R
authors.lastname: Depoortère
authors.forename: Laurent
authors.initials: L
authors.lastname: Bardin
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003080:Cold Temperature; D003250:Constriction; D003521:Cyclopropanes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy*; D000078764:Milnacipran; D009437:Neuralgia / Q000188:drug therapy*; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries; D013997:Time Factors
chemical_list: D000700:Analgesics; D003521:Cyclopropanes; D000639:Amitriptyline; D000078764:Milnacipran