title: The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K(+)ATP pathway.
abstract: BACKGROUND
  Magnesium and MK-801 (dizocilpine), antagonists of N-methyl-d-aspartate receptors, are involved in the processing of pain.
  
  
  OBJECTIVE
  This study determines whether magnesium sulfate (MS) and MK-801 affects visceral inflammatory pain and determines a possible mechanism of action.
  
  
  METHODS
  Analgesic activity was assessed using the acetic acid-induced writhing test in rats. MS (1-45 mg/kg) or MK-801 (0.005-0.03 mg/kg) was administrated subcutaneously (s.c.). To assess possible mechanisms of action, we examined the effects of l-NAME (10 mg/kg, intraperitoneal), methylene blue (0.5 mg/kg, s.c.), and glibenclamide (3 mg/kg, s.c.) on the effect of MS or MK-801.
  
  
  RESULTS
  MS and MK-801 showed biphasic and linear dose-response pattern, respectively. MS reduces the number of writhing on the dose of 1, 5, and 15 mg/kg by 60, 50, and 78%, respectively, while it has no effects on the doses of 30 and 45 mg/kg. MK-801 (0.005-0.03 mg/kg) showed decrease in the number of writhing by 33-79%. The mean effective doses of MS and MK-801 were 6.6 (first phase) and 0.009 mg/kg, respectively. Both drugs did not impair the rotarod performance. l-NAME, methylene blue, and glybenclamide reduced the effect of MK-801 by 100, 43, and 64%, respectively, but not the effect of MS.
  
  
  CONCLUSIONS
  The results suggest that MS and MK-801 may be useful analgesics in the management of visceral inflammatory pain, at doses that do not induce motor impairment. The modulation of NO/cGMP/K+ATP pathway plays an important role in the antinociceptive mechanism of MK-801, but does not contribute to the antinociceptive effect of MS.
authors: Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade , Belgrade , Serbia.
authors: Sonja
authors: S
authors: Vuckovic
authors: Dragana
authors: D
authors: Srebro
authors: Katarina
authors: K
authors: Savic Vujovic
authors: Milica
authors: M
authors: Prostran
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D008278:Magnesium Sulfate / Q000008:administration & dosage*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D059265:Visceral Pain / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000700:Analgesics; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D008278:Magnesium Sulfate; D000255:Adenosine Triphosphate; D006152:Cyclic GMP
keywords: Acetic acid-induced writhing; NMDA antagonist; nitric oxide; rotarod