title: Anti-inflammatory and antinociceptive action of the dimeric enkephalin peptide biphalin in the mouse model of colitis: new potential treatment of abdominal pain associated with inflammatory bowel diseases.
abstract: Biphalin, a mixed MOP/DOP agonist, displays a potent antinociceptive activity in numerous animal models of pain. The aim of the study was to characterize the anti-inflammatory and antinociceptive action of biphalin in the mouse models of colitis. The anti-inflammatory effect of biphalin (5mg/kg, twice daily, i.c. and i.p.) was characterized in a semi-chronic mouse model of colitis, induced by i.c. injection of trinitrobenzenesulfonic acid (TNBS). The antinociceptive action of biphalin (5mg/kg, i.p. and i.c.) in inflamed mice was assessed in mustard oil-induced model of visceral pain and in the hot plate test. In the semi-chronic mouse model of colitis, biphalin i.c. (5mg/kg), but not i.p. improved colitis macroscopic score (2.88±0.19 and 4.99±0.80 units for biphalin and vehicle treated animals, respectively). Biphalin injected i.p. and i.c. (5mg/kg) displayed a potent antinociceptive action in the mustard oil-induced pain test. In the hot plate test, biphalin (5mg/kg, i.p.) produced a potent antinociceptive activity in inflamed mice, suggesting central site of action. Our data suggest that biphalin may become a novel opioid-based analgesic agent in IBD therapy and warrant further investigation of its pharmacological profile.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Sobczak
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pilarczyk
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Jonakowski
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Jarmuż
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Sałaga
authors.affiliation: Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Andrzej W
authors.initials: AW
authors.lastname: Lipkowski
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland; Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. Electronic address: jakub.fichna@umed.lodz.pl.
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced / Q000188:drug therapy*; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004745:Enkephalins / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009149:Mustard Plant; D010938:Plant Oils; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004745:Enkephalins; D010938:Plant Oils; C053673:biphalin; D014302:Trinitrobenzenesulfonic Acid; C027793:mustard oil
keywords: Biphalin; Inflammatory bowel diseases; Inflammatory pain; Mixed opioid agonist; Opioid receptors