Anti-hyperalgesic effect of systemic magnesium sulfate in carrageenan-induced inflammatory pain in rats: influence of the nitric oxide pathway

Abstract

This study investigated whether systemic magnesium sulfate (an antagonist at the glutamate subtype of N-methyl-D-aspartate receptor) affects inflammatory pain, and whether the nitric oxide pathway is involved. Carrageenan (0.5%, 0.1 mL, intraplantar)-induced mechanical hyperalgesia was evaluated using the electronic von Frey test in male Wistar rats. Magnesium sulfate had no effect when injected locally into the inflamed rat paw. However, subcutaneous magnesium sulfate, at doses of 0.5, 5, 15 and 30 mg/kg, reduced the hyperalgesia by 44.4 ± 8.8, 68 ± 8.4, 24.6 ± 6.9 and 45.3 ± 6.7% respectively. N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (3 and 5 mg/kg, intraperitoneal), a non-selective nitric oxide synthase inhibitor, significantly reduced the effects of magnesium sulfate. Also, L-arginine (0.4 mg/kg, subcutaneously) significantly reversed the effect of L-NAME in the magnesium sulfate-treated rats. A selective inhibitor of neuronal or inducible nitric oxide synthase, N-Propyl-L-arginine hydrochloride (L-NPA) (0.5, 1 and 2 mg/kg, intraperitoneal) and S-methylisothiourea (SMT) (0.005, 0.01 and 0.015 mg/kg, intraperitoneal) reduced the effect of magnesium sulfate significantly only at the highest doses tested. When given alone, L-NAME (3 and 5 mg/kg) L-NPA (2 mg/kg) and SMT (0.015 mg/kg) did not have any influence on carrageenaninduced hyperalgesia. The present study revealed that magnesium sulfate is effective against inflammatory pain after systemic, but not after local peripheral administration, and activation of the nitric oxide pathway is probably involved in the anti-hyperalgesic effect of magnesium sulfate. Low doses of systemic magnesium sulfate given as a pretreatment or a treatment might have a beneficial effect in patients with inflammatory somatic pain.

Ketamine versus Ketamine / magnesium Sulfate for Procedural Sedation and Analgesia in the Emergency Department: A Randomized Clinical Trial

“…[ 34 35 ] The other reported mechanisms for MgSO 4 were, reduce the activity of presynaptic and postsynaptic calcium channels and to modulate the release of neurotransmitters, also influencing membrane potentials by exhibits modulator effects on sodium and potassium currents. [ 11 13 ] In the other hand, ketamine interacts with calcium and sodium channels, cholinergic transmission, dopamine receptors, and anti-inflammatory effects. [ 36 ] Hence, further studies with large samples are suggested to assess the effectiveness of different doses of MgSO 4 in combination with ketamine for PSA in the emergency department setting.…”

“…Magnesium sulfate (MgSO 4 ) is an endogenous voltage-dependent NMDA receptor channel blocker. [ 11 12 ] In different types of pain in humans and animals,[ 13 14 15 ] it has been demonstrated that MgSO 4 alone has an analgesic effect. [ 16 17 18 ]…”

Effects of magnesium sulfate on apoptosis in cultured human gastric epithelial cells

“…This suggested that MgSO 4 did not alter the sensitivity of parietal cells to gastrin (Christiansen, Rehfeld, & Stadil, 1975). MgSO 4 has been reported to show an anti-hyperalgesic effect involving activation of the nitric oxide pathway (Srebro, Vučković, Vujović, & Prostran, 2014) .…”

Intracerebroventricular Coadministration of Protoxin-II and Trace Elements in Rats Enhances the Analgesic Effect of the 1.7 Voltage-Gate Sodium Channel Blocker

“…Moreover, Mg ions may influence the pain through a number of diverse pathways [44] including the following: (1) decrease in NMDA action, (2) reducing the synthesis of P substance and its action in the dorsal horn, (3) potency of morphine in the presynaptic part of the dorsal horn, (4) a reduction in the action of some calcium channels in the central nervous system, and (5) a reduction in thromboxane A2 or in the synthesis of certain cytokines for the peripheral system [40,[43][44][45][46][47][48][49][50].…”

“…Chloride. Some models of pain have revealed that exogenous application of zinc has an antihyperalgesic effect [20,47,51]. Even though the Zn modulation pathways of pain are multiple and complex, it is known to control the functions of many pain-related ions channels, including ASICs [52], voltage-gated Ca 2+ and Κ + channels [53], and NMDA receptors [48,51].…”