Articles

Effects of Combining Methylprednisolone with Magnesium Sulfate on Neuropathic Pain and Functional Recovery Following Spinal Cord Injury in Male Rats

Abstract

Methylprednisolone (MP) has been widely used as a standard therapeutic agent for the treatment of spinal cord injury (SCI). Because of its controversial useful effects, the combination of MP and other pharmacological agents to enhance neuroprotective effects is desirable. Magnesium sulfate (MgSO4) has been shown to have neuroprotective and antihyperalgesic effects. In the present study, we sought to determine the effect of combining MP and MgSO4, on neuropathic pain and functional recovery following spinal cord injury (SCI) in male rats. A total of 48 adult male rats (weight 300-350 g) were used. After laminectomy, complete SCI was achieved by compression of the spinal cord for one minute with aneurysm clips. Single doses of Magnesium sulfate (MgSO4), (600 mg/kg), Methylprednisolone (MP), (30 mg/kg) or combining MgSO4 and MP were injected intraperitoneally. Prior to surgery and during four weeks of study Tail flick latency (TFL) and BBB (Basso-Beattie-Bresnahan) score and the acetone drop test were evaluated. In mean values of BBB score, a significant difference was observed in SCI+veh compared with other groups (P<0.05). Mean TFL also was significantly higher in SCI+veh compared with other groups (P<0.05). Mean acetone drop test score and weight were significantly different in MgSO4, MP and combining MgSO4 and MP  treated groups compared with SCI+veh group (P<0.05). These findings revealed that MP, MgSO4 and combining MgSO4 and MP treatment can attenuate neuropathic pains following SCI in rats include: thermal hyperalgesia and cold allodynia. They also can yield better improvement in motor function and decrease weight loss after SCI in rats compared with the control group.

Baastrup C, Finnerup NB. Pharmacological management of neuropathic pain following spinal cord injury. CNS Drugs 2008;22(6):455-75.

Finnerup NB, Baastrup C. Spinal cord injury pain: mechanisms and management. Curr Pain Headache Rep 2012;16(3):207-16.

Peter Vellman W, Hawkes AP, Lammertse DP. Administration of corticosteroids for acute spinal cord injury: the current practice of trauma medical directors and emergency medical system physician advisors. Spine (Phila Pa 1976) 2003;28(9):941-7.

Braus DF, Krauss JK, Strobel J. The shoulder-hand syndrome after stroke: a prospective clinical trial. Ann Neurol 1994;36(5):728-33.

Christensen K, Jensen EM, Noer I. The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Acta Chir Scand 1982;148(8):653-5.

Kotani N, Kushikata T, Hashimoto H, et al. Intrathecal methylprednisolone for intractable postherpetic neuralgia. N Engl J Med 2000;343(21):1514-9.

Takeda K, Sawamura S, Sekiyama H, et al. Effect of methylprednisolone on neuropathic pain and spinal glial activation in rats. Anesthesiology 2004;100(5):1249-57.

Kingery WS, Agashe GS, Sawamura S, et al. Glucocorticoid inhibition of neuropathic hyperalgesia and spinal FOS expression. Anesth Analg 2001;92(2):476-82.

Yin Y, Sun W, Li Z, et al. Effects of combining methylprednisolone with rolipram on functional recovery in adult rats following spinal cord injury. Neurochem Int 2013;62(7):903-12.

Ji B, Li M, Budel S, et al. Effect of combined treatment with methylprednisolone and soluble Nogo-66 receptor after rat spinal cord injury. Eur J Neurosci 2005;22(3):587-94.

Vink R, Cernak I. Regulation of intracellular free magnesium in central nervous system injury. Front Biosci 2000;5:D656-65.

Memon Z, Altura B, Benjamin J, et al. Predictive value of serum ionized but not total magnesium levels in head injuries. Scand J Clin Lab Invest 1995;55(8):671-7.

Temkin NR, Anderson GD, Winn HR, et al. Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial. Lancet Neurol 2007;6(1):29-38.

Bareyre FM, Saatman KE, Raghupathi R, et al. Postinjury treatment with magnesium chloride attenuates cortical damage after traumatic brain injury in rats. J Neurotrauma 2000;17(11):1029-39.

Saatman KE, Bareyre FM, Grady MS, et al. Acute cytoskeletal alterations and cell death induced by experimental brain injury are attenuated by magnesium treatment and exacerbated by magnesium deficiency. J J Neuropathol Exp Neurol 2001;60(2):183-94.

Dubray C, Alloui A, Bardin L, et al. Magnesium deficiency induces a hyperalgesia reversed by the NMDA receptor antagonist MK801. Neuroreport 1997;8(6):1383-6.

Weissberg N, Schwartz G, Shemesh O, et al. Serum and intracellular electrolytes in patients with and without pain. Magnes Res 1991;4(1):49-52.

Rondon LJ, Privat AM, Daulhac L, et al. Magnesium attenuates chronic hypersensitivity and spinal cord NMDA receptor phosphorylation in a rat model of diabetic neuropathic pain. J Physiol 2010;588(Pt 21):4205-15.

Wiseman DB, Dailey AT, Lundin D, et al. Magnesium efficacy in a rat spinal cord injury model. J Neurosurg Spine 2009;10(4):308-14.

Paquette J, Olmstead M. Ultra-low dose naltrexone enhances cannabinoid-induced antinociception. Behav Pharmacol 2005;16(8):597-603.

Basso DM, Beattie MS, Bresnahan JC. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 1996;139(2):244-56.

Kaptanoglu E, Beskonakli E, Okutan O, et al. Effect of magnesium sulphate in experimental spinal cord injury: evaluation with ultrastructural findings and early clinical results. J Clin Neurosci 2003;10(3):329-34.

Kauppila T. Cold exposure enhances tactile allodynia transiently in mononeuropathic rats. Exp Neurol 2000;161(2):740-4.

Ulugol A, Aslantas A, Ipci Y, Tet al. Combined systemic administration of morphine and magnesium sulfate attenuates pain-related behavior in mononeuropathic rats. Brain Res 2002;943(1):101-4.

Lazarini F, Tham TN, Casanova P, et al. Role of the alphachemokine stromal cell-derived factor (SDF-1) in the developing and mature central nervous system. Glia 2003;42(2):139-48.

Yezierski RP, Green M, Murphy K, et al. Effects of gabapentin on thermal sensitivity following spinal nerve ligation or spinal cord compression. Behav Pharmacol 2013 Aug 21. [Epub ahead of print]

Tesiorowski M, Potaczek T, Jasiewicz B, et al. Methylprednisolone- acute spinal cord injury, benefits or risks? Postepy Hig Med Dosw (Online) 2013;67:601-9.

Simpson JI, Eide TR, Schiff GA, et al. Intrathecal magnesium sulfate protects the spinal cord from ischemic injury during thoracic aortic cross-clamping. Anesthesiology 1994;81(6):1493-9.

Gok B, Okutan O, Beskonakli E, et al. Effects of magnesium sulphate following spinal cord injury in rats. Chin J Physiol 2007;50(2):93-7.

Wolf G, Fischer S, Hass P, et al. Magnesium sulphate subcutaneously injected protects against kainate-induced convulsions and neurodegeneration: in vivo study on the rat hippocampus. Neuroscience 1991;43(1):31-4.

Lang-Lazdunski L, Heurteaux C, Dupont H, et al. Prevention of ischemic spinal cord injury: comparative effects of magnesium sulfate and riluzole. J Vasc Surg 2000;32(1):179-89.

Lemke M, Yum SW, Faden AI. Lipid alterations correlate with tissue magnesium decrease following impact trauma in rabbit spinal cord. Mol Chem Neuropathol 1990;12(3):147-65.

Suzer T, Coskun E, Islekel H, et al. Neuroprotective effect of magnesium on lipid peroxidation and axonal function after experimental spinal cord injury. Spinal Cord= 1999;37(7):480-4.

Kaptanoglu E, Beskonakli E, Solaroglu I, et al. Magnesium sulfate treatment in experimental spinal cord injury: emphasis on vascular changes and early clinical results. Neurosurg Rev 2003;26(4):283-7.

Kohno H, Ishida A, Imamaki M, et al. Efficacy and vasodilatory benefit of magnesium prophylaxis for protection against spinal cord ischemia. Ann Vasc Surg 2007;21(3):352-9.

Marsala M, Yaksh TL. Transient spinal ischemia in the rat: characterization of behavioral and histopathological consequences as a function of the duration of aortic occlusion. J Cereb Blood Flow Metab 1994;14(3):526-35.

Chengke L, Weiwei L, Xiyang W, et al. Effect of infliximab combined with methylprednisolone on expressions of NF-kappaB, TRADD, and FADD in rat acute spinal cord injury. Spine (Phila Pa 1976) 2013;38(14):E861-9.

Crosby V, Wilcock A, Mrcp D, et al. The safety and efficacy of a single dose (500 mg or 1 g) of intravenous magnesium sulfate in neuropathic pain poorly responsive to strong opioid analgesics in patients with cancer. J Pain Symptom Manage 2000;19(1):35-9.

Hasanein P, Parviz M, Keshavarz M, et al. Oral magnesium administration prevents thermal hyperalgesia induced by diabetes in rats. Diabetes Res Clin Pract 2006;73(1):17-22.

Song JW, Lee Y-W, Yoon KB, et al. Magnesium sulfate prevents remifentanil-induced postoperative hyperalgesia in patients undergoing thyroidectomy. Anesth Analg 2011;113(2):390-7.

Xiao-Jun X, Jing-Xia H, Seiger Å,et al. Chronic painrelated behaviors in spinally injured rats: Evidence for functional alterations of the endogenous cholecystokinin and opioid systems. Pain 1994;56(3):271-7.

Mert T, Gunes Y, Ozcengiz D, et al. Magnesium modifies fentanyl-induced local antinociception and hyperalgesia. Naunyn Schmiedebergs Arch Pharmacol 2009;380(5):415-20.

Johansson A, Bennett GJ. Effect of local methylprednisolone on pain in a nerve injury model: a pilot study. Reg Anesth 1997;22(1):59-65.

Takeda K, Sawamura S, Sekiyama H, et al. Effect of methylprednisolone on neuropathic pain and spinal glial activation in rats. Anesthesiology 2004;100(5):1249-57.

Kingery WS, Castellote JM, Maze M. Methylprednisolone prevents the development of autotomy and neuropathic edema in rats, but has no effect on nociceptive thresholds. Pain 1999;80(3):555-66.

Lindsey AE, LoVerso RL, Tovar CA, et al. An analysis of changes in sensory thresholds to mild tactile and cold stimuli after experimental spinal cord injury in the rat. Neurorehabil Neural Repair 2000;14(4):287-300.

Sakurai M, Egashira N, Kawashiri T, et al. Oxaliplatininduced neuropathy in the rat: Involvement of oxalate in cold hyperalgesia but not mechanical allodynia. Pain 2009;147(1-3):165-74.

Hayashi R, Xiao W, Kawamoto M, et al. Systemic glucocorticoid therapy reduces pain and the number of endoneurial tumor necrosis factor-alpha (TNFα)-positive mast cells in rats with a painful peripheral neuropathy. J Pharmacol Sci 2008;106(4):559-65.

Han S, Yeo S, Lee M, et al. Early dexamethasone relieves trigeminal neuropathic pain. J Dent Res 2010;89(9):915-20.

Christensen K, Jensen E, Noer I. The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Acta Chir Scand 1981;148(8):653-5.

Zuo Y, Perkins NM, Tracey DJ, et al. Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells. Pain 2003;105(3):467-79.

Theodosiou M, Rush R, Zhou X, et al. Hyperalgesia due to nerve damage: role of nerve growth factor. Pain 1999;81(3):245-55.

Mayer ML, Westbrook GL, Guthrie PB. Voltagedependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 1984;309(5965):261-3.

Regan RF, Jasper E, Guo Y, et al. The effect of magnesium on oxidative neuronal injury in vitro. J Neurochem 1998;70(1):77-85.

Peker S, Abacioglu U, Sun I, et al. Prophylactic effects of magnesium and vitamin E in rat spinal cord radiation damage: evaluation based on lipid peroxidation levels. Life Sci 2004;75(12):1523-30.

Dickens B, Weglicki W, Li Y-S, Mak I. Magnesium deficiency in vitro enhances free radical-induced intracellular oxidation and cytotoxicity in endothelial cells. FEBS Lett 1992;311(3):187-91.

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IssueVol 53, No 3 (2015) QRcode
SectionArticles
Keywords
Spinal cord injury Hyperalgesia Tail flick Neuropathic pain Magnesium sulfate

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How to Cite
1.
Farsi L, Naghib Zadeh M, Afshari K, Norouzi-Javidan A, Ghajarzadeh M, Naghshband Z, Keshavarz M. Effects of Combining Methylprednisolone with Magnesium Sulfate on Neuropathic Pain and Functional Recovery Following Spinal Cord Injury in Male Rats. Acta Med Iran. 1;53(3):149-157.