Magnesium sulfate reduces formalin-induced orofacial pain in rats with normal magnesium serum levels

Srebro, Dragana; Vučković, Sonja; Dožić, Ivan; Dozic, Branko; Vujović, Katarina R. Savić; Milovanović, Aleksandar; Karadzic, Branislav; Prostran, Milica

doi:10.1016/j.pharep.2017.08.005

Cited by 9 publications

(20 citation statements)

References 29 publications

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“…Since inflammatory pain develops after trauma, surgery and rheumatic or arthritic diseases, this pain is the most commonly treated clinical pain. Our results are in agreement with other studies showing that both tramadol ( Garlicki et al, 2006 ; Pecikoza et al, 2017) and magnesium sulfate ( Srebro et al, 2014a , Vuckovic et al, 2015 ; Srebro et al, 2018a ) have an analgesic effect in inflammation. Alexa et al (2015) showed that magnesium enhanced the analgesic effect of tramadol in thermal nociceptive tests without inflammation or neuropathy.…”

Section: Discussionsupporting

confidence: 94%

“…Since both tramadol and magnesium are possible central nervous system depressants, it is important to note that the analgesic dose of tramadol (1.25 mg/kg) (Pecikoza et al, 2017) and magnesium sulfate (30 mg/kg) ( Vuckovic et al, 2015 ) used in the present study do not alter motor coordination. Previously, we showed that the doses of magnesium sulfate used herein did not change the serum concentration of magnesium above the referent range ( Srebro et al, 2018a ), and they did not result in an increase in plasma magnesium concentration above the toxic 3 mM concentration ( Felsby et al, 1996 ). Also, as hypomagnesaemia is associated with the onset of inflammation or can worsen it, we previously showed that our experimental rats had a normal basal blood magnesium concentration ( Srebro et al, 2018a ).…”

Section: Discussionmentioning

confidence: 72%

“…Magnesium is a trace element that acts as a cofactor of enzymes, as a regulator of transmembrane ion fluxes by pumps, carriers and channels, and as a regulator of neurotransmitter (e.g., acetylcholine, norepinephrine) release, participating in metabolic processes, protein synthesis, vasodilatation and neuromuscular excitability ( Shimosawa et al, 2004 ; Guiet-Bara et al, 2007 ). Our previous results showed that magnesium as a single drug in a single dose of magnesium sulfate has analgesic effect in somatic and visceral inflammatory pain ( Srebro et al, 2014a , Vuckovic et al, 2015 ; Srebro et al, 2018a ). The analgesic effect is produced after systemic, but not after local peripheral administration ( Srebro et al, 2014a ).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Prophylactic and Therapeutic Effects of Tramadol and Tramadol Plus Magnesium Sulfate in an Acute Inflammatory Model of Pain and Edema in Rats

et al. 2018

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Background: Inflammatory pain is the most commonly treated clinical pain, since it develops following trauma or surgery, and accompanies rheumatic or arthritic diseases. Tramadol is one of the most frequently used opioid analgesics in acute and chronic pain of different origin. Magnesium is a widely used dietary supplement that was recently shown to be a safe analgesic drug in different models of inflammatory pain.Aim: This study aimed to evaluate the effects of systemically or locally injected tramadol with/without systemically injected magnesium sulfate in prophylactic or therapeutic protocols of application in a rat model of somatic inflammation.Methods: Inflammation of the rat hind paw was induced by an intraplantar injection of carrageenan (0.1 ml, 0.5%). The antihyperalgesic/antiedematous effects of tramadol (intraperitoneally or intraplantarly injected), and tramadol-magnesium sulfate (subcutaneously injected) combinations were assessed by measuring the changes in paw withdrawal thresholds or paw volume induced by carrageenan. The drugs were administered before or after inflammation induction.Results: Systemically administered tramadol (1.25–10 mg/kg) before or after induction of inflammation reduced mechanical hyperalgesia and edema with a maximal antihyperalgesic/antiedematous effect of about 40–100%. Locally applied tramadol (0.125 mg/paw) better reduced edema (50–100%) than pain (20–50%) during 24 h. Administration of a fixed dose of tramadol (1.25 mg/kg) with different doses of magnesium led to a dose-dependent enhancement and prolongation of the analgesic effect of tramadol both in prevention and treatment of inflammatory pain. Magnesium increases the antiedematous effect of tramadol in the prevention of inflammatory edema while reducing it in treatment.Conclusion: According to results obtained in this animal model, systemic administration of low doses of tramadol and magnesium sulfate given in combination is a potent, effective and relatively safe therapeutic option for prevention and especially therapy of somatic inflammatory pain. The best result is achieved when tramadol is combined with magnesium sulfate at a dose that is equivalent to the average human recommended daily dose and when the drugs are administered when inflammation is maximally developed.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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Evaluation of Prophylactic and Therapeutic Effects of Tramadol and Tramadol Plus Magnesium Sulfate in an Acute Inflammatory Model of Pain and Edema in Rats

et al. 2018

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“…In our study, we did not find significant association of lower serum magnesium levels in patient with lung cancer. However, level of magnesium in other disease may be in the normal range, and that magnesium can have an effect on this disease [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Serum magnesium levels and lung cancer risk: a meta-analysis

et al. 2018

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BackgroundWhether serum magnesium levels were lower in patients with lung cancer than that in healthy controls is controversial. The aim of this study was to identify and synthesize all citations evaluating the relationship between serum magnesium levels and lung cancer.MethodsWe searched PubMed, WanFang, China National Knowledge Internet (CNKI), and SinoMed databases for relevant studies before December 31, 2017. Two authors independently selected studies, extracted data, and assessed risk of bias.ResultsEleven citations comprising 707 cases with lung cancer and 7595 healthy controls were included in our study. Serum magnesium levels were not significantly lower in patients with lung cancer [summary SMD = 0.193, 95%CI = − 1.504 to 1.890] when compared to health controls, with significant heterogeneity (I2 = 99.6%, P < 0.001) found. Negative associations were found among Asian populations [summary SMD = 0.229, 95%CI = − 1.637 to 2.094] and European populations [summary SMD = − 0.168, 95%CI = − 0.482 to 0.147]. No publication bias was found using the test of Egger and funnel plot.ConclusionsOur study suggested that serum magnesium levels had no significant association on lung cancer risk.

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“…It should, however, be noted that magnesium sulfate proved inadequate for procedural sedation when combined with ketamine in a recent randomized clinical trial (Azizkhani et al, 2018). Magnesium salts have been used as an adjunct to clinical anesthesia (Elsersy et al, 2017; Elsonbaty and Isonbaty, 2017), and may attenuate vincristine-induced neuropathic pain (Bujalska et al, 2009) and chronic diabetic neuropathic pain (Rondon et al, 2010) in rat models, where they have also been found to reduce inflammatory pain (Srebro et al, 2018), probably due to the blocking action of Mg 2+ on NMDA receptors. Such receptors are well known both in cephalopods (Di Cosmo et al, 2004, 2006) and gastropods (Moccia et al, 2009).…”

Section: Actions Of Anesthetics On Cephalopod Molluscsmentioning

confidence: 99%

Sense and Insensibility – An Appraisal of the Effects of Clinical Anesthetics on Gastropod and Cephalopod Molluscs as a Step to Improved Welfare of Cephalopods

et al. 2018

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Recent progress in animal welfare legislation stresses the need to treat cephalopod molluscs, such as Octopus vulgaris, humanely, to have regard for their wellbeing and to reduce their pain and suffering resulting from experimental procedures. Thus, appropriate measures for their sedation and analgesia are being introduced. Clinical anesthetics are renowned for their ability to produce unconsciousness in vertebrate species, but their exact mechanisms of action still elude investigators. In vertebrates it can prove difficult to specify the differences of response of particular neuron types given the multiplicity of neurons in the CNS. However, gastropod molluscs such as Aplysia, Lymnaea, or Helix, with their large uniquely identifiable nerve cells, make studies on the cellular, subcellular, network and behavioral actions of anesthetics much more feasible, particularly as identified cells may also be studied in culture, isolated from the rest of the nervous system. To date, the sorts of study outlined above have never been performed on cephalopods in the same way as on gastropods. However, criteria previously applied to gastropods and vertebrates have proved successful in developing a method for humanely anesthetizing Octopus with clinical doses of isoflurane, i.e., changes in respiratory rate, color pattern and withdrawal responses. However, in the long term, further refinements will be needed, including recordings from the CNS of intact animals in the presence of a variety of different anesthetic agents and their adjuvants. Clues as to their likely responsiveness to other appropriate anesthetic agents and muscle relaxants can be gained from background studies on gastropods such as Lymnaea, given their evolutionary history.

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Magnesium sulfate reduces formalin-induced orofacial pain in rats with normal magnesium serum levels

Abstract: Preemptive systemic administration of magnesium sulfate as the only drug can be used to prevent inflammatory pain in the orofacial region. Its analgesic effect is not associated with magnesium deficiency.

Cited by 9 publications

References 29 publications

Evaluation of Prophylactic and Therapeutic Effects of Tramadol and Tramadol Plus Magnesium Sulfate in an Acute Inflammatory Model of Pain and Edema in Rats

Evaluation of Prophylactic and Therapeutic Effects of Tramadol and Tramadol Plus Magnesium Sulfate in an Acute Inflammatory Model of Pain and Edema in Rats

Serum magnesium levels and lung cancer risk: a meta-analysis

Sense and Insensibility – An Appraisal of the Effects of Clinical Anesthetics on Gastropod and Cephalopod Molluscs as a Step to Improved Welfare of Cephalopods

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