Ameliorative effect of combined administration of inducible nitric oxide synthase inhibitor with cyclooxygenase-2 inhibitors in neuropathic pain in rats.
OBJECTIVE
The objective of this study was to examine the effects of rofecoxib, meloxicam, both cyclooxygenase-2 (COX-2) inhibitors and aminoguanidine hydrochloride, an inducible nitric oxide synthase (iNOS) inhibitor and their combinations in neuropathic pain in rats.


METHODS
Neuropathy was induced by chronic constriction injury (CCI) of right sciatic nerve under ketamine anesthesia in rats. Effect of ED(50) of aminoguanidine hydrochloride, rofecoxib and meloxicam administered orally was investigated using behavioral tests. Effect of combinations of aminoguanidine hydrochloride with rofecoxib and meloxicam was also investigated in neuropathic pain employing behavioral tests.


RESULTS
Behavioral tests, mechanical, thermal and cold stimuli confirmed the development of neuropathic pain after CCI. Aminoguanidine hydrochloride, rofecoxib and meloxicam when administered alone, produced significant increase in paw withdrawal threshold to mechanical stimuli at 6 h in ipsilateral hind paw after CCI. Co-administration of aminoguanidine hydrochloride (30 mg/kg) with rofecoxib (1.31 mg/kg) and meloxicam (1.34 mg/kg) was also found to produce significant increase in paw withdrawal latencies to mechanical stimuli at 6 h. Combined administration of aminoguanidine hydrochloride with meloxicam and rofecoxib produced significant rise in pain threshold for mechanical hyperalgesia in ipsilateral hind paw when compared with the groups treated with aminoguanidine hydrochloride, meloxicam and rofecoxib alone.


CONCLUSIONS
Co-administration of meloxicam and rofecoxib with aminoguanidine hydrochloride may be an alternative approach for the treatment of neuropathic pain.
Dudhgaonkar
Shailesh P
SP
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Bareilly, Izatnagar 243 122, UP, India.
Tandan
Surendra K
SK
Kumar
Dinesh
D
Naik
Ajit K
AK
Raviprakash
V
V
D000818:Animals; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D000077239:Meloxicam; D009437:Neuralgia / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use; D013843:Thiazines / Q000494:pharmacology / Q000627:therapeutic use; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D052246:Cyclooxygenase 2 Inhibitors; D004338:Drug Combinations; D006146:Guanidines; D007783:Lactones; D013450:Sulfones; D013843:Thiazines; D013844:Thiazoles; C116926:rofecoxib; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D000077239:Meloxicam