Montelukast, a cysteinyl leukotriene receptor antagonist, exerts local antinociception in animal model of pain through the L-arginine/nitric oxide/cyclic GMP/K_ATP channel pathway and PPARγ receptors

Abstract

Objective

The leukotrienes are inflammatory mediators. In the present study, the analgesic role of local montelukast, a cysteinyl leukotriene receptor antagonist, and the possible involvement of L-arginine/NO/cGMP/K_ATP channel pathway and PPARγ receptors was assessed in the formalin test in rats.

Methods and results

The local administration of montelukast into the hind paw produced dose-related analgesia during both phases of the formalin test. Furthermore, pre-treatment with L-NAME, methylene blue, and glibenclamide prevented montelukast (10 μg/paw)-induced antinociception in both early and late phases of the test. Moreover, the local L-arginine and diazoxide before the sub-effective dose of montelukast (3 μg/paw) produced an analgesic effect. Also, local GW-9662 blocked antinociception induced by montelukast plus pioglitazone (10 μg/paw).

Conclusion

In conclusion, montelukast produced peripheral analgesia through PPARγ receptors and activation of the L-arginine/NO/cGMP/K_ATP channel pathway, with potential for a new topical analgesic drug.

Keywords:

• Montelukast
• local antinociception
• L-arginine/NO/cGMP/KATP channel
• PPARγ receptors
• formalin test
• rat

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This article is issued from the medical thesis (Ehsan Alizamani), and financial support was provided by the Vice Chancellor of Research, Dezful University of Medical Sciences (IR.DUMS.REC.1396.20), Dezful, Iran.