title: Antinociceptive effects of gabapentin & its mechanism of action in experimental animal studies.
abstract: OBJECTIVE
  Several studies have shown the possible analgesic effects of gabapentin, widely used as an antiepileptic. Thus, clinical studies have been carried out especially for neuropathic syndroms. This study was undertaken to investigate experimentally whether gabapentin has analgesic effects in mice and rats.
  
  
  METHODS
  The mice were divided into 10 groups (n=7) with various treatments to assess central and peripheral antinociceptive activity of gabapentin. Hot plate, tail clip and tail flick tests were applied for the investigation of central antinociceptive activity and the writhing test was applied for the investigation of peripheral antinociceptive activity. In addition, we also evaluated the levels of PGE 2 and nNOS on perfused hippocampus slices of rats.
  
  
  RESULTS
  Gabapentin showed a peripheral antinociceptive effect at all doses and a central antinociceptive effect at 30mg/kg dose. While the L-NAME and cyproheptadine changed the central and peripheral effects of gabapentin, naloxone did not change these effects. In vitro studies showed that gabapentin significantly increased nNOS level. PGE 2 and nNOS were found to have an important role in the antinociceptive effects of gabapentin at all doses and its combinations with L-NAME, cyproheptadine, indomethacine, and naloxone. As expected, PGE 2 levels decreased in all groups, while nNOS levels increased, which is believed to be an adaptation mechanism.
  
  
  CONCLUSIONS
  Our findings indicate that arachidonate, nitrergic and serotonergic systems play an important role in the antinociceptive activity of gabapentin except for the opioidergic system. Additionally, this effect occured centrally and peripherally. These effects were also mediated by nNOS and PGE2.
authors: Department of Pharmacology, Eşkisehir Osmangazi University, Medical School, Eşkisehir, Turkey.
authors: Fatma Sultan
authors: FS
authors: Kilic
authors: Basar
authors: B
authors: Sirmagul
authors: Engin
authors: E
authors: Yildirim
authors: Setenay
authors: S
authors: Oner
authors: Kevser
authors: K
authors: Erol
mesh_terms: D000588:Amines / Q000008:administration & dosage*; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage*; D015232:Dinoprostone / Q000378:metabolism; D000077206:Gabapentin; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage*
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D052248:Nitric Oxide Synthase Type I; D015232:Dinoprostone