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

• Autorzy: Savic Vujovic K. , Vuckovic S. , Vasovic D. , Medic B. , Knezevic N. , Prostran M.
• Języki publikacji: EN

Abstrakty

EN

Because ketamine and magnesium block NMDA receptor activation by distinct mechanisms of action, we hypothesized that in a model of inflammatory pain in rats the combination of ketamine and magnesium might be more effective than ketamine alone. Antinociceptive activity was assessed by the formalin test in male Wistar rats (200–250 g). Animals were injected with 100 μL of 2.5% formalin to the plantar surface of the right hind paw. Data were recorded as the total time spent in pain‑related behavior after the injection of formalin or vehicle (0.9% NaCl). Ketamine and magnesium sulfate given separately reduced nocifensive behavior in the second phase of the formalin test in rats. When ketamine was applied after magnesium sulfate, the log dose‑response curves for the effects of ketamine and the magnesium sulfate‑ketamine combination revealed antagonistic interaction, and about 1.6 (CL 1.2–2.4) fold increment in ketamine dosage. A low dose of magnesium sulfate (5 mg/kg, subcutaneously) administered after ketamine increased the antinociceptive effect of ketamine by a factor of only 1.2 (CL 0.95–1.38), indicating an additive interaction. There was a 1.8‑fold reduction in dosage of ketamine when ketamine was administered before rather than after the magnesium sulfate. The present study revealed that both ketamine and magnesium reduced pain‑related behavior in the second phase of the formalin test in rats. Ketamine, when administered before or after the magnesium, provided additive or antagonistic antinociceptive interactions, respectively. Whether there will be an additive or antagonistic antinociceptive interaction between ketamine and magnesium depends on the order of drug administration.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: 2
• Opis fizyczny: p.137-146,fig.,ref.

Twórcy

autor

Savic Vujovic K.

• Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

autor

Vuckovic S.

• Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

autor

Vasovic D.

• Faculty of Medicine, University of Belgrade, Belgrade, Serbia

autor

Medic B.

• Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

autor

Knezevic N.

• Department of Anesthesiology, Advocate Illinois Masonic Medical Center, Chicago, IL, USA
• Department of Anesthesiology, University of Illinois, Chicago, IL, USA

autor

Prostran M.

• Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

Bibliografia

• Alvarez P, Saavedra G, Hernández A, Paeile C, Pelissier T (2003) Synergistic antinociceptive effects of ketamine and morphine in the orofacial capsaicin test in the rat. Anesthesiology 99: 969–975.
• Bara M, Guiet‑Bara A, Durlach J (1993) Regulation of sodium and potassium pathways by magnesium in cell membranes. Magnes Res 6: 167–177.
• Begon S, Pickering G, Eschalier A, Dubray C (2002) Magnesium increases morphine analgesic effect in different experimental models of pain. Anesthesiology 96: 627–632.
• Begon S, Pickering G, Eschalier A, Mazur A, Rayssiguier Y, Dubray C (2001) Role of spinal NMDA receptors, protein kinase C and nitric oxide synthase in the hyperalgesia induced by magnesium deficiency in rats. Br J Pharmacol 134: 1227–1236.
• Bujalska‑Zadrożny M, Tatarkiewicz J, Kulik K, Malgorzata F, Naruszewicz M (2016) Magnesium enchances opioid‑induced analgesia – What we have learnt in the past decades? Eur J Pharm Sci 99: 113–127.
• Bulutcu F, Dogrul A, Güç MO (2002) The involvement of nitric oxide in the analgesic effects of ketamine. Life Sci 71: 841–853.
• Cavalcante AL, Siqueira RM, Araujo JC, Gondim DV, Ribeiro RA, Quetz JS, Havt A, Lima AA, Vale ML (2013) Role of NMDA receptors in the trigeminal pathway, and the modulatory effect of magnesium in a  model of rat temporomandibular joint arthritis. Eur J Oral Sci 121: 573–583.
• Chen X, Shu S, Bayliss DA (2009) HCN1 channel subunits are a molecular substrate for hypnotic actions of ketamine. J Neurosci 29: 600–609.
• De Kock M, Lavand’homme P, Waterloos H (2001) ‘Balanced analgesia’ in the perioperative period: Is there a place for ketamine? Pain 92: 373–380.
• DeRossi R, Pompermeyer CT, Silva‑Neto AB, Barros AL, Jardim PH, Frazílio FO (2012) Lumbosacral epidural magnesium prolongs ketamine analgesia in conscious sheep. Acta Cir Bras 27: 137–143.
• do Vale EM, Xavier CC, Nogueira BG, Campos BC, de Aquino PE, da Costa RO, Leal LK, de Vasconcelos SM, Neves KR, de Barros Viana GS (2016) Antinociceptive and Anti‑Inflammatory Effects of Ketamine and the Relationship to Its Antidepressant Action and GSK3 Inhibition. Basic Clin Pharmacol Toxicol 119: 562–573.
• Dubray C, Alloui A, Bardin L, Rock E, Mazur A, Rayssiguier Y, Eschalier A, Lavarenne J (1997) Magnesium deficiency induces an hyperalgesia reversed by the NMDA receptor antagonist MK801. Neuroreport 8: 1383–1386.
• Gaitan G, Herrero JF (2002) Subeffective doses of dexketoprofen trometamol enhance the potency and duration of fentanyl antinociception. Br J Pharmacol 135: 393–398.
• Guiet‑Bara A, Durlach J, Bara  M (2007) Magnesium ions and ionic channels: activation, inhibition or block – a  hypothesis. Magnes Res 20: 100–106.
• Hasanein P, Parviz M, Keshavarz M, Javanmardi K, Mansoori M, Soltani N (2006) Oral magnesium administration prevents thermal hyperalgesia induced by diabetes in rats. Diabetes Res Clin Pract 73: 17–22.
• Herroeder S, Schönherr ME, De Hert SG, Hollmann MW (2011) Magnesium – essentials for anesthesiologists. Anesthesiology 114: 971–993.
• Hirota K, Lambert DG (2011) Ketamine: new uses for an old drug? Br J Anaesth 107: 123–126.
• Irifune  M, Shimizu T, Nomoto  M, Fukuda T (1992) Ketamine‑induced anesthesia involves the N‑methyl‑d‑aspartate receptor‑channel complex in mice. Brain Res 596: 1–9.
• Ishizaki K, Sasaki M, Karasawa S, Obata H, Nara T, Goto F (1999) The effect of intrathecal magnesium sulphate on nociception in rat acute pain models. Anaesthesia 54: 241–246.
• Jabbour HJ, Naccache NM, Jawish RJ, AbouZeid HA, Jabbour KB, Rabbaa‑Khabbaz LG, Ghanem IB, Yazbeck PH (2014) Ketamine and magnesium association reduces morphine consumption after scoliosis surgery: prospective randomised double‑blind study. Acta Anaesthesiol Scand 58: 572–579.
• Jahangiri L, Kesmati M, Najafzadeh H (2013) Evaluation of analgesic and anti‑inflammatory effect of nanoparticles of magnesium oxide in mice with and without ketamine. Eur Rev Med Pharmacol Sci 17: 2706–2710.
• Jiménez‑Andrade JM, Ortiz MI, Pérez‑Urizar J, Aguirre‑Bañuelos P, Granados‑Soto  V, Castañeda‑Hernández G (2003) Synergistic effects between codeine and diclofenac after local, spinal and systemic administration. Pharmacol Biochem Behav 76: 463–471.
• Kapur S, Seeman P (2002) NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5‑HT(2) receptors‑implications for models of schizophrenia. Mol Psychiatry 7: 837–844.
• Koizuka S, Obata H, Sasaki  M, Saito S, Goto F (2005) Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats. Can J Anaesth 52: 498e505.
• Latremoliere A, Woolf CJ (2009) Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 10: 895–926.
• Liu HT, Hollmann MW, Liu WH, Hoenemann CW, Durieux ME (2001) Modulation of NMDA receptor function by ketamine and magnesium: Part I. Anesth Analg 92: 1173–1181.
• Lu WY, Xiong ZG, Orser BA, MacDonald JF (1998) Multiple sites of action of neomycin, Mg2+ and spermine on the NMDA receptors of rat hippocampal CA1 pyramidal neurones. J Physiol 512: 29–46.
• Macdonald FF, Bartlett MC, Mody I, Pahapill P, Reynolds JN, Salter  MW, Schneiderman JH, Pennefather PS (1991) Action of ketamine, phencyclidine and MK‑801 on NMDA receptor currents in cultured mouse hippocampal neurones. J Physiol 432: 483–508.
• Mak DO, Foskett JK (1998) Effects of divalent cations on single‑channel conduction properties of Xenopus IP3 receptor. Am J Physiol 275(1 Pt 1): C179–C188.
• Makau CM, Towett PK, Abelson KS, Kanui TI (2014) Intrathecal administration of clonidine or yohimbine decreases the nociceptive behavior caused by formalin injection in the marsh terrapin (Pelomedusasubrufa). Brain Behav 4: 850–857.
• Matsuda H, Saigusa A, Irisawa H (1987) Ohmic conductance through the inwardly rectifying K channel and blocking by internal Mg2+. Nature 325: 156–159.
• Mcnamara CR, Mandel‑Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM (2007) TRPA1 mediates formalin‑induced pain. Proc Natl AcadSci U S A 104: 13525–13530.
• Mion G, Villevieille T (2013) Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS Neurosci Ther 19: 370–380.
• Mony  L, Kew JN, Gunthorpe MJ, Paoletti P (2009) Allosteric modulators of NR2B‑containing NMDA receptors: molecular mechanisms and therapeutic potential. Br J Pharmacol 157: 1301–1317.
• Niesters M, Martini C, Dahan A (2014) Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol 77: 357–367.
• Orser B, Smith D, Henderson S, Gelb A (1997a) Magnesium deficiency increases ketamine sensitivity in rats. Can J Anaesth 44: 883–890.
• Orser BA, Pennefather PS, MacDonald JF (1997b) Multiple mechanisms of ketamine blockade of N‑methyl‑D‑aspartate receptors. Anesthesiology 86: 903–917.
• Øye I (1998) Ketamine analgesia, NMDA receptors and the gates perception. Acta Anaesthesiol Scand 42: 747–749.
• Pacheco Dda F, Romero TR, Duarte ID (2014) Central antinociception induced by ketamine is mediated by endogenous opioids and µ‑ and δ‑opioid receptors. Brain Res 1562: 69–75.
• Petrenko AB, Yamakura T, Askalany AR, Kohno T, Sakimura K, Baba H (2006) Effects of ketamine on acute somatic nociception in wild‑type and N‑methyl‑D‑aspartate (NMDA) receptor epsilon1 subunit knockout mice. Neuropharmacology 50: 741–747.
• Pitcher GM, Henry JL (2002) Second phase of formalin‑induced excitation of spinal dorsal horn neurons in spinalized rats is reversed by sciatic nerve block. Eur J Neurosci 15: 1509–1515.
• Quibell R, Prommer EE, Mihalyo M, Twycross R, Wilcock A (2011) Ketamine*. J Pain Symptom Manage 41: 640–649.
• Rodríguez‑Muñoz  M, Sánchez‑Blázquez P, Vicente‑Sánchez A, Berrocoso E, Garzón J (2012) The mu‑opioid receptor and the NMDA receptor associate in PAG neurons: implications in pain control. Neuropsychopharmacology 37: 338–349.
• Sarton E, Teppema LJ, Olievier C, Nieuwenhuijs D, Matthes HW, Kieffer BL, Dahan A (2001) The involvement of the mu‑opioid receptor in ketamine‑induced respiratory depression and antinociception. Anesth Analg 93: 1495–1500.
• Savic Vujovic K, Vučković S, Srebro D, Medic B, Stojanovic R, Vucetic Č, Prostran  M (2015) A synergistic interaction between magnesium sulphate and ketamine on the inhibition of acute nociception in rats. Eur Rev Med Pharmacol Sci 19: 2503–2509.
• Sawynok J, Reid A (2002) Modulation of formalin‑induced behaviors and edema by local and systemic administration of dextromethorphan, memantine and ketamine. Eur J Pharmacol 450: 153–162.
• Scheller M, Bufler J, Hertle I, Schneck HJ, Franke C, Kochs E (1996) Ketamine blocks currents through mammalian nicotinic acetylcholine receptor channels by interaction with both the open and the closed state. Anesth Analg 83: 830–836.
• Schulz‑Stübner S, Wettmann G, Reyle‑Hahn SM, Rossaint R (2001) Magnesium as part of balanced general anaesthesia with propofol, remifentenil and mivacurium: a double‑blind, randomized prospective study in 50 patients. Eur J Anaesthesiol 18: 723–729.
• Shi J, Cui J (2001) Intracellular Mg(2+) enhances the function of BK‑type Ca(2+)‑activated K(+) channels. J Gen Physiol 118: 589–606.
• Shi J, Krishnamoorthy G, Yang Y, Hu  L, Chaturvedi N, Harilal D, Qin J, Cui J (2002) Mechanism of magnesium activation of calcium‑activated potassium channels. Nature 418: 876–880.
• Shimosawa T, Takano K, Ando K, Fujita T (2004) Magnesium inhibits norepinephrine release by blocking N‑type calcium channels at peripheral sympathetic nerve endings. Hypertension 44: 897–902.
• Shimoyama  M, Shimoyama N, Gorman AL, Elliott KJ, Inturrisi CE (1999) Oral ketamine is antinociceptive in the rat formalin test: role of the metabolite, norketamine. Pain 81: 85–93.
• Srebro DP, Vučković S, Vujovic KS, Prostran  M (2014) Anti‑hyperalgesic effect of systemic magnesium sulfate in carrageenan‑induced inflammatory pain in rats: influence of the nitric oxide pathway. Magnes Res 27: 77–85.
• Stessel B, Ovink JK, Theunissen HM, Kessels AG, Marcus MA, Gramke H (2013) Is s‑ketamine with or without magnesium sulphate an alternative for postoperative pain treatment? Randomised study. Eur J Anaesthesiol 30: 91–93.
• Takano Y, Sato E, Kaneko T, Sato I (2000) Antihyperalgesic effects of intrathecally administered magnesium sulfate in rats. Pain 84: 175–179.
• Tallarida RJ (2000) Drug Synergism and Dose‑Effect Data Analysis (1st ed). Chapman & Hall/CRC, Boca Raton, FL, USA. Tallarida RJ, Murray RB (1986) Manual of Pharmacologic Calculations with Computer Program (2nd ed.). Springer Verlag, New York, USA. Tjølsen A, Berge OG, Hunskaar S, Rosland JH, Hole K (1992) The formalin test: an evaluation of the method. Pain 51: 5–17.
• Tso MM, Blatchford KL, Callado LF, McLaughlin DP, Stamford JA (2004) Stereoselective effects of ketamine on dopamine, serotonin and noradrenaline release and uptake in rat brain slices. Neurochem Int 44: 1‑7.0.
• Voscopoulos C, Lema  M (2010) When does acute pain become chronic? Br J Anaesth 105: 69–85.
• Vučković S, Savić Vujović K, Srebro D, Medić B, Vučetić C, Prostran  M, Prostran  M (2014) Synergistic interaction between ketamine and magnesium in lowering body temperature in rats. Physiol Behav 127: 45–53.
• Vuckovic S, Srebro D, Savic Vujovic K, Prostran  M (2015a) The antinociceptive effects of magnesium sulfate and MK‑801 in visceral inflammatory pain model: The role of NO/cGMP/K+ATP pathway. Pharm Biol 53: 1621–1627.
• Vučković SM, Savić Vujović KR, Srebro DP, Medić BM, Stojanović RM, Vučetić CS, Divac N, Prostran MS (2015b) The antinociceptive efficacy of morphine‑ketamine‑magnesium combination is influenced by the order of medication administration. Eur Rev Med Pharmacol Sci 19: 3286–3294.
• YamakuraT, Chavez‑Noriega LE, Harris RA (2000) Subunit‑dependent inhibition of human neuronal nicotinic acetylcholine receptors and other ligand‑gated ion channels by dissociative anesthetics ketamine and dizocilpine. Anesthesiology 92: 1144e53.
• Zhu S, Paoletti P (2015) Allosteric modulators of NMDA receptors: multiple sites and mechanisms. Curr Opin Pharmacol 20: 14–23.
• Ziv NY, Tal  M, Shavit Y (2016) The transition from naïve to primed nociceptive state: a novel wind‑up protocol in mice. Exp Neurol 275 Pt 1: 133–142.