title: The neuronal NO synthase participation in the peripheral antinociception mechanism induced by several analgesic drugs.
abstract: The production of nitric oxide (NO) from l-arginine is catalyzed by NO synthase (NOS), which exists as the following three isoforms: endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). The participation of this pathway in peripheral antinociception has been extensively established by our group with the use of several types of drugs, including opioids, cannabinoids, cholinergic, and α(2C) adrenoceptor agonists and nonsteroidal anti-inflammatory drugs (NSAIDS), and even non-pharmacological procedures such as electroacupuncture. In this study, we aimed to refine the previous data to investigate which type of NOS isoform is involved in the peripheral antinociception mechanism induced by anandamide, morphine, SNC80, bremazocine, acetylcholine, xylazine, baclofen, dipyrone, and diclofenac. After hyperalgesia was induced by intraplantar injection of prostaglandin E(2) in male Wistar rats, we measured peripheral nociception with the paw pressure test. All drugs that were used induced a peripheral antinociception effect that was completely blocked by injection of the selective neuronal NO synthase inhibitor, L-NPA (24μg/paw). The exception was the GABA(B) agonist baclofen, which induced an effect that was not antagonized. We used the inhibitors L-NIO and -NIL (24μg/paw) to exclude the involvement of endothelial and inducible NO synthase, respectively. These drugs were ineffective against the antinociception effect induced by all analgesic drugs that we utilized. Based on the experimental evidence, we conclude that the local injection of analgesic drugs activates nNOS to release NO and induce peripheral antinociception.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos, 6627 Pampulha, CEP 31.270-100, Belo Horizonte, MG, Brazil.
authors.forename: Thiago R L
authors.initials: TR
authors.lastname: Romero
authors.forename: Lívia C
authors.initials: LC
authors.lastname: Resende
authors.forename: Igor D G
authors.initials: ID
authors.lastname: Duarte
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D001095:Arachidonic Acids; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D007527:Isoenzymes; C109599:N(omega)-propylarginine; D053284:Polyunsaturated Alkamides; D009569:Nitric Oxide; D001120:Arginine; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D015232:Dinoprostone; D000109:Acetylcholine; C078814:anandamide