title: Influence of nitric oxide synthase or cyclooxygenase inhibitors on cannabinoids activity in streptozotocin-induced neuropathy.
abstract: BACKGROUND
  Influence of a relatively specific inhibitor cyclooxygenase (COX)-2, celecoxib, a relatively specific inhibitor of neuronal nitric oxide synthase (NOS), 7-Ni, and a relatively selective inhibitor of inducible NOS, L-NIL, on the action of a preferentially selective CB1 cannabinoid receptor agonist, Met-F-AEA and a selective CB2 cannabinoid receptor agonist, AM 1241 was investigated, in a streptozotocin (STZ)-induced neuropathy.
  
  
  METHODS
  Studies were performed on male Wistar rats. Changes in nociceptive thresholds were determined using mechanical stimuli - the modification of the classic paw withdrawal test described by Randall-Selitto. Diabetes was induced by a single administration of STZ.
  
  
  RESULTS
  In a diabetic neuropathic pain model, pretreatment with celecoxib, L-NIL and 7-Ni, significantly increased the antihyperalgesic activity of both Met-F-AEA and AM 1241.
  
  
  CONCLUSIONS
  The results of this study seemed to indicate that the interaction between cannabinoid, COX-2 and NOS(s) systems might exist. Concomitant administration of small doses of CB1 and/or CB2 receptor agonists and COX-2 or NOS inhibitors can be effective in the alleviation of diabetic neuropathic pain.
authors.affiliation: Department of Pharmacodynamics, Medical University of Warsaw, Warszawa, Poland. Electronic address: mbujalska@gmail.com.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bujalska-Zadrożny
authors.affiliation: Department of Pharmacodynamics, Medical University of Warsaw, Warszawa, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: de Cordé
authors.affiliation: Department of Pharmacodynamics, Medical University of Warsaw, Warszawa, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Pawlik
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology / Q000627:therapeutic use; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D000068579:Celecoxib / Q000494:pharmacology / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D003929:Diabetic Neuropathies / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D004357:Drug Synergism; D006930:Hyperalgesia / Q000188:drug therapy; D007191:Indazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: C443759:2-methylarachidonyl-2'-fluoroethylamide; C439263:AM 1241; D001095:Arachidonic Acids; D002186:Cannabinoids; D016861:Cyclooxygenase Inhibitors; D007191:Indazoles; C090663:N(6)-(1-iminoethyl)lysine; D013311:Streptozocin; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D000068579:Celecoxib; D008239:Lysine; C080122:7-nitroindazole
keywords: Cannabinoid system; Cyclooxygenase; Diabetes; Hyperalgesia; Nitric oxide synthase