title: The effect of nitric oxide synthase inhibitors on the development of analgesic tolerance to dipyrone in mice.
abstract: Recent investigations have shown that, similarly to opioids, tolerance develops to the analgesic effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Nitric oxide has been shown to play an important role in opioid-induced analgesic tolerance; we, therefore, planned to determine if nitric oxide also plays role in the analgesic tolerance to dipyrone, a NSAID. Using the hot-plate test in mice, an analgesic tolerance developed to dipyrone with its 150 and 300 mg/kg intraperitoneal doses after 7 days; no tolerance was observed with its dose of 600 mg/kg. Neither 7-nitroindazole (50 mg/kg, i.p.), a neuronal NOS inhibitor, nor aminoguanidine (30 mg/kg, i.p.), an inducible NOS inhibitor, had any effect on dipyrone-induced analgesic tolerance with doses, which also had no analgesic effect when used alone. Our results show that nitric oxide does not play role in the analgesic tolerance to dipyrone; however, further experiments are required to delineate the mechanisms and to take preventive measures against this problem, which will possibly limit the use of NSAIDs.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Trakya University, Edirne, Turkey.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yilmaz
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ulugol