dizocilpine-maleate and Visceral-Pain

Previously we described the antinociceptive effect of magnesium sulfate and dizocilpine (MK-801) in the visceral and somatic rat models of pain. In the somatic model of pain, we established the influence of selective inhibitors of neuronal and inducible nitric oxide synthase on the antihyperalgesic effects of magnesium sulfate and dizocilpine. Therefore, the objective of the present study was to determine in the rat model of visceral pain whether same mechanisms are involved in the antinociceptive action of magnesium sulfate and dizocilpine. Analgesic activity was assessed using the acetic acid-induced writhing test in rats. Subcutaneous injection of either magnesium sulfate (15 mg/kg) or dizocilpine (0.01 mg/kg) decreased the number of writhes by about 60 and 70%, respectively. The role of nitric oxide on the effects of magnesium sulfate and dizocilpine was evaluated using selective inhibitor of neuronal (N-ω-Propyl-L-arginine hydrochloride (L-NPA)) and inducible (S-methylisothiourea (SMT)) nitric oxide synthase, which per se did not affect the number of writhes. We observed that the antinociceptive effect of magnesium sulfate or dizocilpine did not change in the presence of L-NPA (2 and 10 mg/kg, i.p.) and SMT (0.015 and 10 mg/kg, i.p.). We conclude that, nitric oxide produced by neuronal and inducible nitric oxide synthase does not modulate the effects of magnesium sulfate and dizocilpine in the visceral inflammatory model of pain in the rat.

Topics: Acetic Acid; Analgesics; Animals; Calcium Channel Blockers; Disease Models, Animal; Dizocilpine Maleate; Dose-Response Relationship, Drug; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Indicators and Reagents; Isothiuronium; Magnesium Sulfate; Male; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Pain Measurement; Rats; Rats, Wistar; Statistics, Nonparametric; Time Factors; Visceral Pain

Magnesium and MK-801 (dizocilpine), antagonists of N-methyl-d-aspartate receptors, are involved in the processing of pain.. This study determines whether magnesium sulfate (MS) and MK-801 affects visceral inflammatory pain and determines a possible mechanism of action.. 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.. 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.. 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.

Topics: Adenosine Triphosphate; Analgesics; Animals; Cyclic GMP; Dizocilpine Maleate; Injections, Subcutaneous; Magnesium Sulfate; Male; Nitric Oxide; Rats; Rats, Wistar; Signal Transduction; Visceral Pain