Study of the Interactions Between Magnesium, Ketamine and Morphine on Acute Nociception in Rats

2017 ◽  
Vol 41 (S1) ◽  
pp. S708-S709
Author(s):  
K. Savic Vujovic ◽  
A. Vujovic ◽  
S. Vuckovic ◽  
B. Medic ◽  
M. Prostran
Keyword(s):  
Magnesium Sulfate ◽  
Magnesium Sulphate ◽  
Wistar Rats ◽  
Antinociceptive Effect ◽  
Immersion Test ◽  
Synergistic Interaction ◽  
Tail Immersion ◽  
Male Wistar Rats ◽  
Competing Interest ◽  
First Time

ObjectivesStudy is aimed at evaluating the effects of ketamine and magnesium sulphate on acute nociceptive pain in rats and examination whether magnesium sulfate added to ketamine or morphine-ketamine combination produces higher level of analgesia.MethodsAnalgesic activity was assessed by tail-immersion test in male Wistar rats (200–250 g).ResultsMagnesium sulfate (2.5–60 mg/kg, s.c.) and ketamine (2.5-30 mg/kg, i.p.) given alone did not produce any effect on antinociception. However, there is a synergistic interaction between ketamine (2.5, 5 and 10 mg/kg) and magnesium sulfate (5 mg/kg). Both ketamine and magnesium sulfate, as well as their combination potentiated the antinociceptive effect of morphine (2.6 mg/kg, i.p.).ConclusionThis study revealed potentiation of ketamine and morphine-ketamine combination by magnesium sulphate in tail-immersion test in rats with higher activity when ketamine is given before magnesium sulfate. It is first time to demonstrate the synergistic interaction between magnesium sulphate and ketamine in lowering body temperature and in antinociception with statistical confirmation.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The Analgesic Efficacy of Ketamine-Magnesium Combination is Influenced by the Order of Medication Administration

2016 ◽  
Vol 33 (S1) ◽  
pp. S503-S503
Author(s):  
K. Savic Vujovic ◽  
S. Vuckovic ◽  
A. Vujovic ◽  
M. Prostran
Keyword(s):  
Nmda Receptor ◽  
Magnesium Sulphate ◽  
Analgesic Efficacy ◽  
Medication Administration ◽  
Immersion Test ◽  
Nmda Receptor Antagonist ◽  
Nociceptive Pain ◽  
Tail Immersion ◽  
Male Wistar Rats ◽  
Competing Interest

IntroductionMagnesium is an endogenous voltage-dependent NMDA receptor channel blocker and ketamine is a non-competitive NMDA receptor antagonist. Magnesium may potentiate the effect of ketamine in analgesia and anaesthesia, but may also interact in an opposing manner. This study aimed at evaluating type of the interaction between magnesium sulphate and ketamine administered systemically in rats with an acute nociceptive pain (tail-immersion test).Materials and methodsAnalgesic activity was assessed by tail-immersion test in male Wistar rats (200-250 g). The distal 5 cm of the tail was immersed in a warm water bath (55 ± 0.5 °C) and the time for tail-withdrawal was measured as response latency.ResultsMagnesium sulphate (2.5–30 mg/kg, s.c.) and ketamine (2.5-30 mg/kg, i.p.) administered alone did not produce any effect. However, significant antinociception (synergistic interaction) was revealed at the following doses of ketamine: magnesium sulphate of 5:5 mg/kg, 2.5:5 mg/kg and 10:5 mg/kg. The effect was not dose-dependent, and a greater response was obtained when ketamine was administered before magnesium sulphate.ConclusionsThis study revealed that (1) magnesium sulphate and ketamine given alone were not effective against acute nociceptive pain in rats, but (2) a combination of both drugs resulted in synergistically inhibited nociception, (3) which occurred only at selected low doses and proportions of the medications in a combination and (4) suggested the importance of the order of drug administration.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Involvement of serotonergic, noradrenergic and gabaergic systems in the antinociceptive effect of a ketamine-magnesium sulfate combination in acute pain

2018 ◽  
Vol 68 (1) ◽  
pp. 108-118 ◽  
Author(s):  
Savić Vujović Katarina ◽  
Vučković Sonja ◽  
Stojanović Radan ◽  
Divac Nevena ◽  
Medić Branislava ◽  
...  
Keyword(s):  
Magnesium Sulfate ◽  
Acute Pain ◽  
Antinociceptive Effect ◽  
Nmda Antagonist ◽  
Anion Channel ◽  
Immersion Test ◽  
Nmda Receptor Antagonist ◽  
Albino Rats ◽  
Dependent Manner ◽  
Tail Immersion

Abstract Ketamine and magnesium can interact in additive, supra-additive and antagonistic manners in analgesia or anesthesia. Ketamine is a non-competitive NMDA receptor antagonist. Magnesium is an endogenous non-competitive NMDA antagonist that causes anion channel blockade in a dose-dependent manner. It has been established that ketamine and magnesium interact synergistically in the tail-immersion test in rats. To determine the role of serotonergic, GABAergic and noradrenergic systems in analgesia induced by the ketamine-magnesium sulfate combination. Experiments were performed on male Wistar albino rats (200-250 g). Antinociception was evaluated by the tail-immersion test. Methysergide (0.5 and 1 mg/kg, sc) administered alone did not affect nociception in rats. Methysergide (0.5 and 1 mg/kg, sc) antagonized the antinociceptive effect of the ketamine (5 mg/kg)-magnesium sulfate (5mg/kg) combination. Bicuculline (0.5 and 1 mg/kg, sc) given alone did not change the threshold to thermal stimuli in rats. Bicuculline (0.5 and 1 mg/kg, sc) antagonized the antinociceptive effect of the ketamine (5 mg/kg)-magnesium sulfate (5 mg/kg) combination. Yohimbine (0.5, 1 and 3 mg/kg, sc) applied alone did not change nociception. Yohimbine at a dose of 0.5 mg/kg did not influence the effect of ketamine (5 mg/kg)-magnesium sulfate (5 mg/kg), while yohimbine at doses of 1 and 3 mg/kg antagonized the antinociceptive effect of this combination. Serotonergic, noradrenergic and GABAergic systems participate, at least in part, in the antinociceptive effect of the ketamine-magnesium sulfate combination in acute pain in rats.

Antitumoral and Anticholinesterasic Activities of the Seven Species from Rubiaceae

2019 ◽  
Vol 20 (4) ◽  
pp. 302-308 ◽  
Author(s):  
Carla R.F. Volobuff ◽  
Pedro C.O. Junior ◽  
Sidney M. dos Santos ◽  
Zefa V. Pereira ◽  
Diego C. Ferreira ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Biological Activities ◽  
Brain Structures ◽  
Acetylcholinesterase Inhibition ◽  
Mato Grosso ◽  
Male Wistar Rats ◽  
First Time ◽  
Mato Grosso Do Sul ◽  
Antiproliferative Activities ◽  
Mcf 7

Background: The genus Psychotria and Palicourea are reported as a source of alkaloids and iridoids, which exhibit biological activities. This study aimed to evaluate antiproliferative and anticholinesterase activities and quantification of the alkaloids of seven species among the genus found in Mato Grosso do Sul region in Brazil. Methods: Concentrations of alkaloids were measured spectrophotometrically. The extracts were submitted to antiproliferative activity against ten cell lines. The anticholinesterase activity of the extracts was developed using brain structures of male Wistar rats: cerebral cortex, hippocampus, hypothalamus and striatum by the Ellman method. Results: Alkaloids from Psychotria and Palicourea species were quantified which showed values of 47.6 to 21.9 µg/g. Regarding the antiproliferative potential, Palicourea crocea demonstrated selectivity against the 786-0 cell line (GI50: 22.87 µg/mL). Psychotria leiocarpa inhibited cell growth against OVCAR-3 (GI50: 3.28 µg/mL), K-562 (GI50: 5.26 µg/mL), HaCaT (GI50: 27.20 µg/mL), PC-3 (GI50: 34.92 µg/mL), MCF-7 (GI50: 35.80 µg/mL) and P. capillacea showed activity against OVCAR-3 (GI50: 2.33 µg/ml) and U251 (GI50: 16.66 µg/ml). The effect of acetylcholinesterase inhibition was more effective in the hippocampus, demonstrating inhibition for Paliourea crocea, Psychotria deflexa, P. brachybotrya and P. leiocarpa of 70%, 57%, 50% and 40%, respectively, followed by P. poeppigiana and P. capillacea, inhibiting 21%, compared to the control. Conclusion: Herein, the present work showed for the first time, anticholinesterasic and antiproliferative activities of extracts of Palicourea and Psychotria seem to be mainly associated with the levels of alkaloids in the leaves of these species.

scholarly journals Bioactivities of the ethanol extract from Ageratum fastigiatum branches: antioxidant, antinociceptive and anti-inflammatory

2016 ◽  
Vol 88 (3) ◽  
pp. 1471-1484
Author(s):  
GLAUCIEMAR DEL-VECHIO-VIEIRA ◽  
BRUNA C.S. SANTOS ◽  
MARIA SILVANA ALVES ◽  
AÍLSON L.A. ARAÚJO ◽  
CÉLIA H. YAMAMOTO ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Folk Medicine ◽  
Reducing Power ◽  
Ethanol Extract ◽  
Immersion Test ◽  
Significant Inhibition ◽  
Paw Edema ◽  
Hot Plate ◽  
Tail Immersion ◽  
Anti Inflammatory

ABSTRACT The present study was designed to investigate the antioxidant, antinociceptive and anti-inflammatory activities of the ethanol extract from Ageratum fastigiatum branches. Phytochemical screening and total phenol and flavonoid contents were determined. The antioxidant activity was assessed by 2,2-diphenyl-1-pycrilhydrazin (DPPH) and iron reducing power methods. The antinociceptive effect was evaluated using the acetic acid-induced writhing, formalin, hot plate and tail immersion assays; while the carrageenan-induced paw edema and pleurisy tests were performed to examine the anti-inflammatory activity against acute inflammation. The extract revealed the presence of flavonoids, tannins, coumarins, terpenes, sterols and saponins. Expressive levels of total phenols and flavonoids and a promising antioxidant effect were quantified. At the doses of 50, 100 and 200 mg/kg, the extract inhibited the writhing, reduced both phases of paw licking time and increased the reaction time on the hot plate. In the tail immersion test, the extract (50, 100 and 200 mg/kg) caused a significant inhibition of pain. In these doses, the paw edema, exudate volume and leucocyte mobilization were significantly reduced. These results suggest that A. fastigiatum can be an active source of substances with antioxidant, antinociceptive and anti-inflammatory activities, adding scientific support to the appropriate use in the Brazilian folk medicine.

Abstract 301: Nebivolol Attenuates Prooxidant and Profibrotic Mechanisms and Decreases Vascular Remodeling in Renovascular Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Carla S Ceron ◽  
Elen Rizzi ◽  
Danielle A Guimaraes ◽  
Alisson Martins-Oliveira ◽  
Raquel F Gerlach ◽  
...  
Keyword(s):  
Vascular Remodeling ◽  
Adrenergic Receptor ◽  
Wistar Rats ◽  
Aortic Wall ◽  
Left Renal Artery ◽  
Male Wistar Rats ◽  
Receptor Blockers ◽  
First Time ◽  
Picrosirius Red ◽  
Metalloproteinase 9

Nebivolol and metoprolol are β1-adrenergic receptor blockers with different properties. We hypothesized that nebivolol, but not metoprolol, could attenuate prooxidant and profibrotic mechanisms of hypertension vascular remodeling. Hypertension was induced in male Wistar rats by clipping the left renal artery. Six weeks after surgery, hypertensive and sham rats were treated with nebivolol (Nebi 10 mg/kg/day), metoprolol (Meto 20 mg/kg/day) or vehicle for four weeks. Systolic blood pressure was monitored weekly. Morphologic changes in the aortic wall were studied in picrosirius red sections. Aortic NAD(P)H activity was evaluated by luminescence. Nitrotyrosine staining was evaluated to assess peroxynitrite formation by immunohistochemistry. TGF-β and matrix metalloproteinase-9 (MMP-9) levels were determined by immunofluorescence, and p-ERK 1/2 expression by western blotting. Both β1-receptor antagonists exerted very similar antihypertensive effects (156 ± 8 mmHg and 151 ± 9 mmHg, respectively, versus 206 ± 7 mmHg in hypertensive controls; both P<0.05). However, while metoprolol had no significant effects, nebivolol significantly (all P<0.05) attenuated vascular collagen surface (237944 ± 59567, 69784 ± 17686, 183215 ± 30338 μm2, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups), attenuated hypertension-induced increases in aortic NAD(P)H oxidase activity (253887 ± 13712, 143765 ± 15642, and 232465 ± 14352 AU, respectively in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups), in nitrotyrosine levels (166.3 ± 2.9, 145.3 ± 1.5, 172.1 ± 7.3 AU, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups), in TGF-β upregulation (7.2 ± 0.12, 6.5 ± 0.03, 7.0 ± 0.3 AU, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups) and in MMP-9 levels (18.27 ± 0.8, 12.73 ± 0.4, 15.76 ± 1.4 AU, respectively in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups). No effects on p-ERK 1/2 expression were found with both drugs (P>0.05) (1.0 ± 0.16, 0.92 ± 0.15, 0.87 ± 0.37 AU, respectively, in the 2K1C, 2K1C+Nebi, and 2K1C+Meto groups). These results show for the first time that nebivolol, but not metoprolol, attenuates prooxidant and profibrotic mechanisms involving TGF-β and MMP-9, which promote vascular remodeling in hypertension.

Modulation of the Nuclear Factor (Erythroid 2-Derived)-Like 2 Pathway by Antidepressants In Rats

2016 ◽  
Vol 33 (S1) ◽  
pp. S527-S527
Author(s):  
D. Martín Hernández ◽  
Á.G. Bris ◽  
K.S. MacDowell ◽  
A. Sayd ◽  
D. Azpiazu ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Wistar Rats ◽  
Nitrosative Stress ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Nuclear Factor ◽  
Nrf2 Pathway ◽  
Antidepressant Treatments ◽  
Male Wistar Rats ◽  
Competing Interest

IntroductionPatients with major depression who are otherwise medically healthy have activated inflammatory pathways. It has been described that depression is not only escorted by inflammation but also by induction of multiple oxidative/nitrosative stress pathways. Nevertheless, there are finely regulated mechanisms involved in preserving cells from damage, such as the nuclear factor Nrf2.AimsTo explore in a depression-like model the Nrf2 pathway in the prefrontal cortex (PFC) and the hippocampus of rats and to analyze which classic antidepressants affect the antioxidant activity of the Nrf2 pathway.MethodsMale Wistar rats were exposed to chronic mild stress (CMS) and some of them were treated with desipramine, escitalopram or duloxetine. We studied the expression in the PFC and hippocampus of upstream and downstream elements of the Nrf2 pathway and the oxidative damage induced by the CMS.ResultsAfter exposure to a CMS protocol, in the PFC, there is an inhibition of upstream and downstream elements of the Nrf2 pathway. Moreover, antidepressant treatments, particularly desipramine and duloxetine, are able to recover some of these elements and to reduce the oxidative damage induced by the depression model. In the hippocampus however, Nrf2 pathways are not that affected and antidepressants do not have many actions.ConclusionsNrf2 pathway is differentially regulated by antidepressants in the PFC and hippocampus. The Nrf2 pathway is involved in the oxidative/nitrosative damage detected in the PFC after CMS exposure. However, it seems that Nrf2 is not very involved in the effects caused by the CMS in the hippocampus.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Quercetin action on pain modulation/ Ação da quercetina sobre a modulação da dor

2021 ◽  
Vol 7 (4) ◽  
pp. 43616-43634
Author(s):  
Maria Elvira Ribeiro Cordeiro ◽  
Flávio Klinpovous Kerppers ◽  
Luiza Ferreira Cunha ◽  
Ketllin Bragnholo ◽  
Luana Rodrigues Vasconcelos ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Immersion Test ◽  
Positive Control ◽  
Pain Modulation ◽  
Antinociceptive Activity ◽  
Formalin Injection ◽  
Immersion Method ◽  
Cholinergic Pathways ◽  
Cholinergic Pathway ◽  
Tail Immersion

Background: Quercetin is a flavonoid widely found in plant kingdom and target of studies in pharmacological area due to its potent antinociceptive effect compared to analgesics used in conventional therapies. The aim was to evaluate its antinociceptive activity and antinociception mechanism. Methods: For this, 40 Norvegicus Wistar rats were used, divided into 4 groups: Q50 (treated with quercetin 50 mg/Kg), Q100 (treated with quercetin 100 mg/Kg), Q500 (treated with quercetin 500 mg/Kg) and Positive control (PC) without quercetin treatment), who were submitted through the pain induction methods by tail immersion and formalin in the first step to assess antinociceptive action and in the second step, tail immersion method receiving antagonists from opioid, cholinergic and nitric oxide - L-arginine to evaluate the action mechanism. Results: Quercetin antinociceptive activity was verified at the dose of 50 mg/kg and 100 mg/kg in tail immersion test after formalin injection, with better performance at the dose of 50 mg/kg. There were no statistically significant results in paw opening and capsaicin tests. Quercetin demonstrated a possible influence on opioid and cholinergic pathway, which was not observed on the nitric acid - L-arginine pathway in view of parameters tested. Conclusion: Quercetin performed the best antinociceptive activity at a dose 50 mg/kg and there was a possible influence on opioid and cholinergic pathways.

scholarly journals EFFECT OF LYOPHILIZED JUICE OF PUNICA GRANATUM L. IN ANTINOCICEPTIVE AND INFLAMMATORY PAIN

2021 ◽  
pp. 17-19
Author(s):  
JOSE ANTONIO GUERRERO-SOLANO ◽  
MIRANDELI BAUTISTA ◽  
NELLY DEL SOCORRO CRUZ-CANSINO ◽  
ALEJANDRO CHEHUE-ROMERO ◽  
OSMAR ANTONIO JARAMILLO-MORALES
Keyword(s):  
Body Weight ◽  
Acetylsalicylic Acid ◽  
Inflammatory Pain ◽  
Wistar Rats ◽  
Formalin Test ◽  
Antinociceptive Effect ◽  
Punica Granatum ◽  
Reference Drug ◽  
Male Wistar Rats ◽  
Punica Granatum L

Objective: The aim of this study was to explore the analgesic activity of lyophilized juice of Punica granatum L., obtained from Hidalgo, Mexico, in theformalin test.Methods: We extracted the juice manually, filtered it and then dried down in a lyophilizer machine. We evaluated the antinociceptive effect oflyophilized juice from pomegranate in the formalin test (2%) in male Wistar rats (180–200 g body weight). Thirty minutes before the test, a dose of316 mg/kg (lyophilized juice) and acetylsalicylic acid as reference drug (100 mg/kg) both were administered intragastrically (i.g.).Results: The oral administration of lyophilized juice of pomegranate showed a significant decrease in the number of flinches in the temporal courseand a significant antinociceptive effect in nociceptive and inflammatory pain compared with the vehicle. In the same way, this effect appeared with thedrug of reference (acetylsalicylic acid 100 mg/kg i.g). Furthermore, it was shown that juice had a 34% of antinociception on overall effect versus vehicle.Conclusion: The results suggest that lyophilized juice of pomegranate has antinociceptive effect in nociceptive and inflammatory pain. Therefore, thisstudy supports the possible use of this lyophilized juice of pomegranate in the treatment of pain.

scholarly journals Pain neuromodulation exerted by Ruta graveolens aqueous extract in experimental models of nociception/ Neuromodulação da dor exercida pela Ruta graveolens extrato aquoso em modelos experimentais de nocicepção

2021 ◽  
Vol 7 (4) ◽  
pp. 43667-43682
Author(s):  
Flávio Klinpovous Kerppers ◽  
Maria Elvira Ribeiro Cordeiro ◽  
Tatiane Budniak Mazur ◽  
Heron Bittencourt ◽  
Karoline Penteado da Luz ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Wistar Rats ◽  
Pain Threshold ◽  
Antinociceptive Effect ◽  
Positive Control ◽  
Experimental Models ◽  
Antinociceptive Activity ◽  
Ruta Graveolens ◽  
Treatment Groups ◽  
Tail Immersion

Introduction: The use of medicinal plants for therapeutic purposes has been common practice since antiquity. Ruta graveolens L., commonly known as rue, has been shown to have antiparasitic, antioxidant, antibacterial and allelopathic activity. Objective: The objective was to investigate the antinociceptive effect of rue, as well as the mechanisms behind this effect. Materials and Methods: The sample consisted of 40 male Norvegicus (Wistar) rats, randomly divided into a positive control and three treatment groups administered Ruta graveolens L. aqueous extract at the following doses: 50 mg/kg, 100 mg/kg or 500 mg/kg, p.o. The experimental models of nociception used in this study to assess effectiveness of the treatments were the formalin and capsaicin tests. Five days prior to nociceptive challenges, the tail immersion assay was conducted to determine baseline pain threshold. Results: Antinociceptive activity was observed at Ruta graveolens L. aqueous extract concentrations of 50 mg/kg and 100mg/kg. 500 mg/kg induced pro-nociceptive activity with activation of the L-arginine-oxide-nitric system. Conclusion: These results suggest Ruta graveolens L. aqueous extract antinociceptive activity, and possible antagonism towards receptors

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