Effect of zileuton in radicular pain induced by herniated nucleus pulposus in rats.
Arachidonic acid metabolites, prostaglandins and leukotrienes are detected in clinical cases of herniated nucleus pulposus. However, little is known about their role in the associated symptoms like radicular pain. The aim of the present study was to examine the role of leukotrienes in an animal model of hyperalgesia induced by application of autologus nucleus pulposus to sciatic nerve in rats. Hyperalgesia was assessed employing noxious mechanical and thermal stimuli. Zileuton, a 5-lipoxygenase inhibitor, dose dependently (25-100 mg/kg, p.o.), and indomethacin (2 mg/kg, p.o.), a non-selective cyclooxygenase inhibitor, significantly (P > 0.05) decreased mechanical as well as thermal hyperalgesia on postoperative days 3, 5 and 7 as compared to the nucleus pulposus group. Further, co-administration of zileuton (25 mg/kg, p.o.) with indomethacin (2 mg/kg, p.o.) showed enhanced anti-hyperalgesic effect in both the paradigms as compared to effect per se. The present study, thus, suggested that leukotrienes as well as prostaglandins might play a significant role in hyperalgesia induced by autologus nucleus pulposus in rats. The results suggested that dual inhibition approach of 5-lipoxygenase and cyclooxygenase enzymes may prove beneficial in such conditions.
Singh
Vijay Pal
VP
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.
Patil
Chandrashekhar S
CS
Kulkarni
Shrinivas K
SK
D000818:Animals; D005260:Female; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D007405:Intervertebral Disc Displacement / Q000188:drug therapy* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017208:Rats, Wistar
C063449:zileuton; D006918:Hydroxyurea