title: Antinociceptive effects of novel melatonin receptor agonists in mouse models of abdominal pain.
abstract: OBJECTIVE
  To characterize the antinociceptive action of the novel melatonin receptor (MT) agonists, Neu-P11 and Neu-P12 in animal models of visceral pain.
  
  
  METHODS
  Visceral pain was induced by intracolonic (ic) application of mustard oil or capsaicin solution or by intraperitoneal (ip) administration of acetic acid. Neu-P11, Neu-P12, or melatonin were given ip or orally and their effects on pain-induced behavioral responses were evaluated. To identify the receptors involved, the non-selective MT1/MT2 receptor antagonist luzindole, the MT2 receptor antagonist 4-P-PDOT, or the μ-opioid receptor antagonist naloxone were injected ip or intracerebroventricularly (icv) prior to the induction of pain.
  
  
  RESULTS
  Orally and ip administered melatonin, Neu-P11, and Neu-P12 reduced pain responses in a dose-dependent manner. Neu-P12 was more effective and displayed longer duration of action compared to melatonin. The antinociceptive effects of Neu-P11 or Neu-P12 were antagonized by ip or icv. administered naloxone. Intracerebroventricularly, but not ip administration of luzindole or 4-P-PDOT blocked the antinociceptive actions of Neu-P11 or Neu-P12.
  
  
  CONCLUSIONS
  Neu-P12 produced the most potent and long-lasting antinociceptive effect. Further development of Neu-P12 for future treatment of abdominal pain seems promising.
authors.affiliation: Chunqiu Chen, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Chunqiu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Chunqiu Chen, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
authors.affiliation: Chunqiu Chen, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Moshe
authors.initials: M
authors.lastname: Laudon
authors.affiliation: Chunqiu Chen, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Martin
authors.initials: M
authors.lastname: Storr
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D011714:Pyrans / Q000008:administration & dosage / Q000494:pharmacology*; D044094:Receptors, Melatonin / Q000819:agonists* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000700:Analgesics; D007211:Indoles; D009292:Narcotic Antagonists; D011714:Pyrans; D044094:Receptors, Melatonin; D008550:Melatonin; C581609:N-(2-(5-methoxy-indol-3-yl)-ethyl)-4-oxo-4H-pyran-2-carboxamide
keywords: Gastrointestinal tract; Melatonin; Neu-P11; Neu-P12; Opioid; Visceral pain