title: The antinociceptive effect and mechanisms of action of pregabalin in mice.
abstract: BACKGROUND
  Pregabalin, a potent anticonvulsant agent, is used in treatment-resistant epileptic patients. It is reported that pregabalin also has analgesic effect in different pain syndromes. However, there is limited data on its antinociceptive mechanisms of action. We aimed to investigate the central and peripheral antinociceptive effects of pregabalin and the contribution of nitrergic, serotonergic, and opioidergic pathways in mice.
  
  
  METHODS
  We used tail flick, tail clip and hot plate tests to investigate the central antinociceptive effects and acetic acid-induced writhing test to assess peripheral antinociceptive effects of pregabalin (10, 30, 100mg/kg). We also combined pregabalin (100mg/kg) with, a nonspecific nitric oxide synthase inhibitor l-NAME (100mg/kg), a serotonin receptor antagonist cyproheptadine (50 μg/kg), and an opioid receptor antagonist naloxone (1mg/kg).
  
  
  RESULTS
  Pregabalin 30 mg/kg enhanced the percentage of maximal possible effect (% MPE) in tail flick test. Pregabalin 100mg/kg significantly increased % MPE in tail clip and tail flick tests and decreased the number of writhings. Pregabalin made no significant alteration in hot plate test at all doses. The combined use of pregabalin 100mg/kg with l-NAME, cyproheptadine, and naloxone showed that % MPE was reduced only in the combination of pregabalin with naloxone and solely in tail clip test while no significant difference was observed in writhing test.
  
  
  CONCLUSIONS
  We suggest that pregabalin (30 and 100mg/kg) presents central spinal but not central supraspinal antinociceptive effect and pregabalin 100mg/kg shows peripheral antinociceptive effect. The opioidergic pathway seems to mediate the central spinal antinociceptive effect of pregabalin while nitrergic and serotonergic pathways are not involved.
authors.affiliation: Eskişehir Osmangazi University, Medical Faculty, Department of Pharmacology, Meselik Kampusu, Eskisehir, Turkey.
authors.forename: Bilgin
authors.initials: B
authors.lastname: Kaygisiz
authors.affiliation: Eskişehir Osmangazi University, Medical Faculty, Department of Pharmacology, Meselik Kampusu, Eskisehir, Turkey. Electronic address: fskilic@ogu.edu.tr.
authors.forename: Fatma Sultan
authors.initials: FS
authors.lastname: Kilic
authors.affiliation: Eskişehir Osmangazi University, Medical Faculty, Department of Pharmacology, Meselik Kampusu, Eskisehir, Turkey.
authors.forename: Nuri
authors.initials: N
authors.lastname: Senguleroglu
authors.affiliation: Eskişehir Osmangazi University, Medical Faculty, Department of Biostatistics, Meselik Kampusu, Eskisehir, Turkey.
authors.forename: Canan
authors.initials: C
authors.lastname: Baydemir
authors.affiliation: Eskişehir Osmangazi University, Medical Faculty, Department of Pharmacology, Meselik Kampusu, Eskisehir, Turkey.
authors.forename: Kevser
authors.initials: K
authors.lastname: Erol
mesh_terms: D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003533:Cyproheptadine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006358:Hot Temperature; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010147:Pain Measurement / Q000187:drug effects; D000069583:Pregabalin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D000700:Analgesics; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D012702:Serotonin Antagonists; D003533:Cyproheptadine; D009270:Naloxone; D000069583:Pregabalin; D019001:Nitric Oxide Synthase; D019342:Acetic Acid; D019331:NG-Nitroarginine Methyl Ester
keywords: Cyproheptadine; Experimental pain; Naloxone; Pregabalin; l-NAME