Dynorphin-mediated antinociceptive effects of l-arginine and SIN-1 (an NO donor) in mice

• Published in: Brain research bulletin Vol. 70; no. 3; pp. 245 - 250
• Main Authors: Chung, Eunhee, Burke, Brianna, Bieber, Andrew J., Doss, Jason C., Ohgami, Yusuke, Quock, Raymond M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.07.2006
• Subjects: Analgesics - administration & dosage; Animals; Antinociception; Arginine; Arginine - administration & dosage; Brain - drug effects; Dynorphin; Dynorphins - drug effects; Dynorphins - metabolism; Enzyme Inhibitors - pharmacology; Injections, Intraventricular; Male; Mice; Molsidomine - administration & dosage; Molsidomine - analogs & derivatives; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; Nitric oxide; Nitric Oxide Donors - administration & dosage; NO donors; Opioid; Pain Measurement; Arginine; Nitric oxide; Dynorphin; Opioid; Antinociception; Mice; NO donors
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2006.05.008

The antinociceptive response of mice to the amino acid l-arginine ( l-ARG) has been attributed to either an opioid mechanism or a non-opioid but nitric oxide (NO)-dependent mechanism. Earlier it was reported that the mechanism of nitrous oxide-induced antinociception involved opioid components and was also dependent on brain NO. This study was designed to determine whether the antinociceptive effects of l-ARG and the NO donor 3-morpholinosydnoimine (SIN-1) might be mediated by brain mechanisms similar to those that are responsible for nitrous oxide (N 2O) antinociception. l-ARG and SIN-1 were administered to mice intracerebroventricularly (i.c.v.), and antinociception was assessed using the acetic acid abdominal constriction test. Both l-ARG and SIN-1 caused dose-related antinociceptive effects that were blocked by naloxone and norbinaltorphimine. The antinociceptive effects of both SIN-1 and l-ARG were also blocked to a greater extent by i.c.v. administration of a rabbit antiserum against rat dynorphin 1–13 than an antiserum against methionine-enkephalin, suggesting that the SIN-1 and l-ARG effects may be related to stimulated release of dynorphin. The antinociceptive effect of l-ARG was antagonized by an inhibitor of neuoronal NO synthase enzyme, indicating that l-ARG had to be converted to NO for its antinociceptive action. These findings indicate that the mechanisms of antinociceptive action of l-ARG and SIN-1 are both mediated by dynorphin and dependent on NO.