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Antinociceptive effects of novel melatonin receptor agonists in mouse models of abdominal pain
Chunqiu Chen1, Jakub Fichna1, Moshe Laudon1
1Chunqiu Chen, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
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.
Insights
Novel melatonin receptor agonists, Neu-P11 and Neu-P12, effectively reduced visceral pain in animal models. Neu-P12 demonstrated superior potency and duration, suggesting potential for abdominal pain treatment.
Area of Science:
- Pharmacology
- Neuroscience
- Pain Research
Background:
- Visceral pain is a significant clinical challenge.
- Melatonin receptors (MT) are implicated in pain modulation.
- Novel MT agonists offer potential therapeutic avenues.
Purpose of the Study:
- To evaluate the antinociceptive effects of Neu-P11 and Neu-P12 in visceral pain models.
- To characterize the receptor mechanisms underlying their action.
Main Methods:
- Visceral pain was induced using chemical irritants (mustard oil, capsaicin, acetic acid).
- Neu-P11, Neu-P12, and melatonin were administered orally or intraperitoneally.
- Receptor involvement was assessed using MT and opioid receptor antagonists (luzindole, 4-P-PDOT, naloxone).
Main Results:
- Both Neu-P11 and Neu-P12 dose-dependently reduced pain responses.
- Neu-P12 exhibited greater efficacy and a longer duration of action than melatonin.
- Antinociceptive effects were blocked by naloxone and central administration of MT antagonists.
Conclusions:
- Neu-P12 demonstrated the most potent and sustained antinociceptive effect.
- These findings support the development of Neu-P12 for treating abdominal pain.
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