Pharmacodynamic evaluation of magnesium sulfate and dizocilpine in models of somatic and visceral pain in rats

Magnezijum je mineral koji u organizmu ima brojne uloge. On je kofaktor u više od 300 enzimskih reakcija, održava membranski potencijal, ima modulatorno dejstvo na jonske kanale, neurotransmisiju, i drugo...Magnesium is a mineral who has many functions in the human body: he is cofactor for 300 enzymatic reaction, modulates ion channels, neurotransmission, etc. Magnesium is an endogenous voltage-dependent N-methyl-D-aspartate (NMDA) receptor channel blocker. Dizocilpine (MK-801) is a noncompetitive NMDA receptor antagonist. Dizocilpine is commonly used as a neuropharmacological tool. The activation of NMDA receptor has a significant role in the development and maintenance of an inflammatory pain. Activation of these receptors may increase the synthesis of nitric oxide (NO). Also, transient receptor potential (TRP) channels and acid sensitive ion channels (ASIC) are important in pain. It is well known that magnesium and dizocilpine can reduce neuropathic pain and enhance analgesic effect of opioids or anesthetics. Aim: The aim of this thesis was to examine whether magnesium sulfate and dizocilpine has analgesic and antiedematous effect in somatic and visceral inflammatory pain in rats and to explore the possible role of NO in the mechanisms of their actions. Methods: Male Wistar rats were used. Carragennan-induced hyperalgesia and edema in rats was used as a model of somatic inflammatory pain. Hyperalgesia was examined by von Fray analgesiometric test. Antiedematous effect was examined by immersing paw in the plethysmometer. The acetic acid-induced writhing test in rats was used as a model of visceral pain. Mechanism of action was evaluated with inhibitors of NOS. Results: In the somatic inflammatory model of pain systemically administered magnesium sulfate reduces hyperalgesia and edema in a dose-independent manner. It is more efficient in lower (5 mg/kg, sc), than in higher doses (15 and 30 mg/kg, sc). The analgesic effect is not present after local peripheral application, as opposed to antiedematous effect that is present after both routes of administration. Magnesium sulfate systematically applied has preventive (given as a pretreatment) and therapeutic (given as treatment) effect on pain and swelling in inflammation. Dizocilpine has dosedependent antihyperalgesic effect after systemical and local peripheral application in the model of somatic inflammation..

Pharmacodynamic evaluation of magnesium sulfate and dizocilpine in models of somatic and visceral pain in rats

Magnezijum je mineral koji u organizmu ima brojne uloge. On je kofaktor u više od 300 enzimskih reakcija, održava membranski potencijal, ima modulatorno dejstvo na jonske kanale, neurotransmisiju, i drugo...Magnesium is a mineral who has many functions in the human body: he is cofactor for 300 enzymatic reaction, modulates ion channels, neurotransmission, etc. Magnesium is an endogenous voltage-dependent N-methyl-D-aspartate (NMDA) receptor channel blocker. Dizocilpine (MK-801) is a noncompetitive NMDA receptor antagonist. Dizocilpine is commonly used as a neuropharmacological tool. The activation of NMDA receptor has a significant role in the development and maintenance of an inflammatory pain. Activation of these receptors may increase the synthesis of nitric oxide (NO). Also, transient receptor potential (TRP) channels and acid sensitive ion channels (ASIC) are important in pain. It is well known that magnesium and dizocilpine can reduce neuropathic pain and enhance analgesic effect of opioids or anesthetics. Aim: The aim of this thesis was to examine whether magnesium sulfate and dizocilpine has analgesic and antiedematous effect in somatic and visceral inflammatory pain in rats and to explore the possible role of NO in the mechanisms of their actions. Methods: Male Wistar rats were used. Carragennan-induced hyperalgesia and edema in rats was used as a model of somatic inflammatory pain. Hyperalgesia was examined by von Fray analgesiometric test. Antiedematous effect was examined by immersing paw in the plethysmometer. The acetic acid-induced writhing test in rats was used as a model of visceral pain. Mechanism of action was evaluated with inhibitors of NOS. Results: In the somatic inflammatory model of pain systemically administered magnesium sulfate reduces hyperalgesia and edema in a dose-independent manner. It is more efficient in lower (5 mg/kg, sc), than in higher doses (15 and 30 mg/kg, sc). The analgesic effect is not present after local peripheral application, as opposed to antiedematous effect that is present after both routes of administration. Magnesium sulfate systematically applied has preventive (given as a pretreatment) and therapeutic (given as treatment) effect on pain and swelling in inflammation. Dizocilpine has dosedependent antihyperalgesic effect after systemical and local peripheral application in the model of somatic inflammation..

Pharmacodynamic evaluation of magnesium sulfate and dizocilpine in models of somatic and visceral pain in rats

Magnezijum je mineral koji u organizmu ima brojne uloge. On je kofaktor u više od 300 enzimskih reakcija, održava membranski potencijal, ima modulatorno dejstvo na jonske kanale, neurotransmisiju, i drugo...Magnesium is a mineral who has many functions in the human body: he is cofactor for 300 enzymatic reaction, modulates ion channels, neurotransmission, etc. Magnesium is an endogenous voltage-dependent N-methyl-D-aspartate (NMDA) receptor channel blocker. Dizocilpine (MK-801) is a noncompetitive NMDA receptor antagonist. Dizocilpine is commonly used as a neuropharmacological tool. The activation of NMDA receptor has a significant role in the development and maintenance of an inflammatory pain. Activation of these receptors may increase the synthesis of nitric oxide (NO). Also, transient receptor potential (TRP) channels and acid sensitive ion channels (ASIC) are important in pain. It is well known that magnesium and dizocilpine can reduce neuropathic pain and enhance analgesic effect of opioids or anesthetics. Aim: The aim of this thesis was to examine whether magnesium sulfate and dizocilpine has analgesic and antiedematous effect in somatic and visceral inflammatory pain in rats and to explore the possible role of NO in the mechanisms of their actions. Methods: Male Wistar rats were used. Carragennan-induced hyperalgesia and edema in rats was used as a model of somatic inflammatory pain. Hyperalgesia was examined by von Fray analgesiometric test. Antiedematous effect was examined by immersing paw in the plethysmometer. The acetic acid-induced writhing test in rats was used as a model of visceral pain. Mechanism of action was evaluated with inhibitors of NOS. Results: In the somatic inflammatory model of pain systemically administered magnesium sulfate reduces hyperalgesia and edema in a dose-independent manner. It is more efficient in lower (5 mg/kg, sc), than in higher doses (15 and 30 mg/kg, sc). The analgesic effect is not present after local peripheral application, as opposed to antiedematous effect that is present after both routes of administration. Magnesium sulfate systematically applied has preventive (given as a pretreatment) and therapeutic (given as treatment) effect on pain and swelling in inflammation. Dizocilpine has dosedependent antihyperalgesic effect after systemical and local peripheral application in the model of somatic inflammation..

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

Background: In humans, orofacial pain has a high prevalence and is often difficult to treat. Magnesium is an essential element in biological a system which controls the activity of many ion channels, neurotransmitters and enzymes. Magnesium produces an antinociceptive effect in neuropathic pain, while in inflammatory pain results are not consistent. We examined the effects of magnesium sulfate using the rat orofacial formalin test, a model of trigeminal pain. Methods: Male Wistar rats were injected with 1.5% formalin into the perinasal area, and the total time spent in pain-related behavior (face rubbing) was quantified. We also spectrophotometrically determined the concentration of magnesium and creatine kinase activity in blood serum. Results: Magnesium sulfate administered subcutaneously (0.005-45 mg/kg) produced significant antinociception in the second phase of the orofacial formalin test in rats at physiological serum concentration of magnesium. The effect was not dose-dependent. The maximum antinociceptive effect of magnesium sulfate was about 50% and was achieved at doses of 15 and 45 mg/kg. Magnesium did not affect increase the levels of serum creatine kinase activity. Conclusions: 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