期刊
WORLD JOURNAL OF GASTROENTEROLOGY
卷 20, 期 5, 页码 1298-1304出版社
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v20.i5.1298
关键词
Gastrointestinal tract; Melatonin; Neu-P11; Neu-P12; Opioid; Visceral pain
资金
- University of Calgary Research Grant Committee
- Deutsche Forschungsgemeinschaft [STO 645/6-1, 645/9-1]
- Iuventus Plus program of the Polish Ministry of Science and Higher Education [0119/IP1/2011/71, 0107/IP1/2013/72]
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 mu-opioid receptor antagonist naloxone were injected ip or intra-cerebroventricularly (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. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
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