The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K⁺ATP pathway

Abstract

Context: 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. Materials and 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.

Analgesic effect and safety of single-dose intra-articular magnesium after arthroscopic surgery: a systematic review and meta-analysis

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Threat Response System: Parallel Brain Processes in Pain vis-à-vis Fear and Anxiety

“…There are other potential psychopharmacological strategies for the management of the reentrant ( 126 ) autonomous thalamocortical circuits ( 105 ). Anti-glutamatergic agents may be helpful ( 127 ) and have already been successfully used in pain patients ( 128 – 130 ). As an example, ketamine administration produces long-term analgesia lasting at least 3 months ( 131 ).…”

Additive and antagonistic antinociceptive interactions between magnesium sulfate and ketamine in the rat formalin test

“…On the contrary, it was demonstrated that intraperitoneal magnesium oxide had an antinociceptive effect in both phases of the formalin test, as well as in the writhing test in mice (Jahangiri et al 2013). Our previous results showed that magnesium sulfate and MK-801 are effective against acetic acid-induced visceral and carrageenan-induced somatic inflammatory pain models in rats (Vuckovic et al 2015a). Unlike MK-801, the effects of magnesium sulfate were not dose-dependent.…”