title: Central antinociceptive effect of tapentadol is increased by nitric oxide synthase inhibitors.
abstract: Nitric oxide synthases (NOSs) have been shown to participate in the mechanism of the antinociceptive action of tapentadol. The results obtained in this study indicate that tapentadol administered intrathecally at a range of doses (30-100 µg) increased nociceptive thresholds in the Randall-Selitto and tail-flick tests in rats; however, this effect was significant only for the higher doses. After intracerebroventricular administration of tapentadol at the same dose range, an antinociceptive effect was observed only in response to mechanical stimuli. In coadministration studies, L-N-nitro arginine (L-NOArg) - a nonselective NOS inhibitor as well as selective inhibitors: 7-Nitroindazole (7-NI), L-N(1-iminoethyl)lysine (L-NIL) or N-(1-iminoethyl)-L-ornithine (L-NIO) for the respective neuronal, inducible, and endothelial NOSs enhanced the antinociceptive activity of intrathecally administered tapentadol in the Randall-Selitto test and to a lesser extent in the tail-flick test. A similar, although less pronounced effect of intracerebroventricular tapentadol was also observed after previous administration of NOS inhibitors in the Randall-Selitto test, but not in the tail-flick test. In conclusion, neuronal NOS, inducible NOS, and endothelial NOS influence the antinociceptive action of tapentadol at the spinal level and to a much lesser extent at the supraspinal level.
authors: aDepartment of Pharmacodynamics, Centre for Preclinical Research and Technology, Faculty of Pharmacy bDepartment of Internal Medicine, Hypertension and Vascular Diseases, Medical University of Warsaw, Warsaw cDepartment of Genomics, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Magdalenka, Poland.
authors: Magdalena
authors: M
authors: Bujalska-Zadrożny
authors: Renata
authors: R
authors: Wolińska
authors: Anna
authors: A
authors: Leśniak
authors: Mariusz
authors: M
authors: Sacharczuk
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D010146:Pain / Q000188:drug therapy*; D017288:Pain Threshold; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D000077432:Tapentadol
chemical_list: D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D010636:Phenols; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D000077432:Tapentadol