Effect of licofelone against mechanical hyperalgesia and cold allodynia in the rat model of incisional pain.
Hyperalgesia from an incisional pain is evoked by noxious stimuli (mechanical and cold). The present study was aimed to examine the effect of licofelone, a dual inhibitor of cyclooxygenases (COX-1/COX-2) and 5-lipoxygenase (5-LOX) against mechanical hyperalgesia and cold allodynia in the rat model of incisional pain. Mechanical hyperalgesia and cold allodynia was assessed employing Randall and Sellitto analgesymeter and cold water maintained at 10 degrees C, respectively. Zileuton (25-100 mg/kg, po), a 5-LOX inhibitor, indomethacin (1-30 mg/kg, po), a non-selective COX inhibitor, and licofelone (10-100 mg/kg, po) a dual inhibitor, significantly reversed the mechanical hyperalgesia and also caused an increase in cold allodynia threshold with different pharmacologic profile. The rank order of potency based on ED50 values in both the paradigms was found to be licofelone > indomethacin > zileuton. The results of the present study are indicative of the role of leukotrienes along with prostaglandins in the rat model of incisional pain (a paradigm of postoperative pain). The results suggested that dual inhibition approach of simultaneous inhibition of COX and LOX pathways might prove beneficial in combating hyperalgesia of postoperative pain.
Singh
Vijay P
VP
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.
Patil
Chandrashekhar S
CS
Kulkarni
Shrinivas K
SK
D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006614:Hindlimb; D006358:Hot Temperature; D006918:Hydroxyurea / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D006930:Hyperalgesia / Q000517:prevention & control*; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000293:injuries; D010149:Postoperative Pain / Q000503:physiopathology / Q000517:prevention & control*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014110:Touch
D000085:Acetates; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D011758:Pyrroles; C088092:licofelone; C063449:zileuton; D006918:Hydroxyurea; D007213:Indomethacin