title: Effect of iNOS inhibitor S-methylisothiourea in monosodium iodoacetate-induced osteoathritic pain: implication for osteoarthritis therapy.
abstract: Much information is available on the role of nitric oxide (NO) in osteoarthritis (OA). However, its role has not been studied in the monosodium iodoacetate (MIA)-induced model of osteoarthritic pain. The present study was undertaken in rats to investigate the effect of iNOS inhibitor S-methylisothiourea (SMT) in MIA-induced osteoathritic pain and disease progression in rats. Osteoarthritis was produced by single intra-articular injection of the MIA in the right knee joint on day 0. Treatment groups were orally gavazed with different doses of SMT (10, 30 and 100mg/kg) and etoricoxib (10mg/kg) daily for 21 days. On days 0, 3, 7, 14 and 21, pain was measured and histopathology of right knee joint was done on day 21. SMT produced analgesia in a dose-dependent manner as shown by mechanical, heat hyperalgesia, knee vocalization, knee squeeze test, and spontaneous motor activity test. SMT reduced NO production in synovial fluid. Histopathological findings indicated that SMT reduced disease progression as evident from complete cartilage formation in rats treated with SMT at 30 mg/kg. In conclusion, the results indicate that SMT attenuates the MIA-induced pain and histopathological changes in the knee joint. The antinociceptive and antiarthritic effects of SMT were mediated by inhibiting cartilage damage and suppression of NO in synovial fluid. It is suggested that SMT has potential as a therapeutic modality in the treatment of osteoarthritis.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, Bareilly, U.P. 243 122, India.
authors.forename: Amar S
authors.initials: AS
authors.lastname: More
authors.forename: Rashmi R
authors.initials: RR
authors.lastname: Kumari
authors.forename: Gaurav
authors.initials: G
authors.lastname: Gupta
authors.forename: Madhu C
authors.initials: MC
authors.lastname: Lingaraju
authors.forename: Venkanna
authors.initials: V
authors.lastname: Balaganur
authors.forename: Nitya N
authors.initials: NN
authors.lastname: Pathak
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Kumar
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Surendra K
authors.initials: SK
authors.lastname: Tandan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007270:Injections, Intra-Articular; D019807:Iodoacetic Acid / Q000633:toxicity*; D007550:Isothiuronium / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010003:Osteoarthritis / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control*; D010146:Pain / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control*; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D007550:Isothiuronium; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C027744:S-methylisothiopseudouronium; D019807:Iodoacetic Acid