Ehsan Alizamani1, Behnam Ghorbanzadeh1,2, Reza Naserzadeh1, Mohammad Taghi Mansouri3. 1. Department of Pharmacology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran. 2. Pain Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 3. Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA.
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/KATP 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/KATP channel pathway, with potential for a new topical analgesic drug.
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/KATP 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/KATP channel pathway, with potential for a new topical analgesic drug.
Entities:
Keywords:
L-arginine/NO/cGMP/KATP channel; Montelukast; PPARγ receptors; formalin test; local antinociception; rat