Brief Article
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World J Gastroenterol. Feb 7, 2014; 20(5): 1298-1304
Published online Feb 7, 2014. doi: 10.3748/wjg.v20.i5.1298
Antinociceptive effects of novel melatonin receptor agonists in mouse models of abdominal pain
Chunqiu Chen, Jakub Fichna, Moshe Laudon, Martin Storr
Chunqiu Chen, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
Jakub Fichna, Department of Biomolecular Chemistry, Medical University of Lodz, 92-215 Lodz, Poland
Moshe Laudon, Neurim Pharmaceuticals LTD, 69710 Tel-Aviv, Israel
Martin Storr, Division of Gastroenterology, Department of Medicine, Ludwig Maximilians University of Munich, 81377 Munich, Germany
Chunqiu Chen, Jakub Fichna, Martin Storr, Division of Gastroenterology, University of Calgary, Calgary AB T2N 4N1, Canada
Author contributions: Laudon M and Storr M designed the study; Chen C and Fichna J acquired and analyzed data; Chen C, Fichna J and Storr M drafted the manuscript; Laudon M and Storr M obtained funding.
Supported by The University of Calgary Research Grant Committee (to Storr M); the Deutsche Forschungsgemeinschaft (STO 645/6-1 and 645/9-1 to Storr M); and the Iuventus Plus program of the Polish Ministry of Science and Higher Education (0119/IP1/2011/71 and 0107/IP1/2013/72 to Fichna J)
Correspondence to: Martin Storr, MD, PhD, Professor, Division of Gastroenterology, Department of Medicine, Ludwig Maximilians University of Munich, Marchioninistrasse 15, 81377 Munich, Germany. martin.storr@med.uni-muenchen.de
Telephone: +1-49-8970950 Fax: +1-49-8970950-5281
Received: August 7, 2013
Revised: September 10, 2013
Accepted: November 3, 2013
Published online: February 7, 2014
Abstract

AIM: 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.

CONCLUSION: Neu-P12 produced the most potent and long-lasting antinociceptive effect. Further development of Neu-P12 for future treatment of abdominal pain seems promising.

Keywords: Gastrointestinal tract, Melatonin, Neu-P11, Neu-P12, Opioid, Visceral pain

Core tip: In search for new efficient therapies for the treatment of pain in the irritable bowel syndrome, the antinociceptive activity of two novel melatonin receptor agonists, Neu-P11 and Neu-P12, was characterized in a well-established mouse model of visceral pain. Neu-P12 produced a potent and long-lasting antinociceptive effect after intraperitoneal and oral administration. Further development of this novel compound for future treatment of abdominal pain seems promising.