title: Effects of milnacipran, duloxetine and indomethacin, in polyarthritic rats using the Randall-Selitto model.
abstract: Milnacipran, a serotonin and noradrenalin reuptake inhibitor (SNRI), is efficacious in rodents in various models of acute or chronic pain (traumatic, neuropathic, inflammatory, visceral). However, its activity against arthritic pain has never been explored. Here, we assessed the activity of acute treatment with milnacipran in a polyarthritic rat model. Rats were injected in the tail base with complete Freund's adjuvant to induce a state of polyarthritis. Analgesic effects of acute treatment with intraperitoneal administration of milnacipran were then evaluated, using the Randall-Selitto model, against two levels of pressure applied to both hind paws (a lower one, addressing mechanical allodynia and a higher one, addressing mechanical hyperalgesia). The other SNRI duloxetine and the nonsteroidal anti-inflammatory drug indomethacin were tested as positive controls. Milnacipran was significantly and dose dependently active against the decrease of paw withdrawal threshold produced by complete Freund's adjuvant for low (minimum effective dose=5 mg/kg, range tested: 2.5-10 mg/kg) and high (minimum effective dose=10 mg/kg, range tested: 5-20 mg/kg)-pressure levels. Duloxetine (20 mg/kg, intraperitoneally) was significantly active against low pressure only. Indomethacin (3 mg/kg per os) was efficacious against both pressure levels. These rodent data suggest that milnacipran should be efficacious in painful conditions associated with chronic inflammatory states, such as arthritis.
authors.affiliation: Department of Neuroscience (Pharmacology and Psychiatry), Faculty of Medicine, University of Cadiz, Cadiz, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Mico
authors.forename: Esther
authors.initials: E
authors.lastname: Berrocoso
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: Laurent
authors.initials: L
authors.lastname: Bardin
authors.forename: Ronan
authors.initials: R
authors.lastname: Depoortère
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D003521:Cyclopropanes / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D000078764:Milnacipran; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003521:Cyclopropanes; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride; D000078764:Milnacipran; D007213:Indomethacin