Intravenous Granulocyte Colony-Stimulating Factor Administration Can Attenuate Neuropathic Pain Following Spinal Cord Injury in Male Rats
Peripheral neuropathy, regularly expressed as hypersensitivity to painful stimuli, is between the most common complications of spinal cord injury (SCI) that develops in up to 40% of patients and appears to be persistent. Previous studies have demonstrated neuroprotective effects of Granulocyte colony-stimulating factor (G-CSF) on neuropathic pains. We aimed to investigate the antihyperalgesic effect of G-CSF on neuropathic pains following SCI in male rats. Twenty four adult male rats (weight 300–350g) were used. After laminectomy, complete SCI was performed by compression of the spinal cord for 1 minute with an aneurysm clip. Within 30 minutes after the surgery, 200 µg/kg G-CSF was injected intravenously in G-CSF treated groups and then was repeated in 3 consecutive days. Tail flick latency (TFL), acetone drop test scores, BBB test scores, and Von-Frey filament test were performed before surgery and once a week after surgery. Rats in G-CSF treated group showed significantly higher mean TFL, and lower mean score of acetone test compared with those in SCI+veh group 4 weeks after surgery (P<0.05). There was no significant difference between rats in G-CSF treated group and SCI+veh group in BBB and Von-Frey filament tests results. These findings revealed that treatment with systemic administration of intravenous G-CSF would attenuate thermal hyperalgesia, and cold allodynia induced by SCI in rats but has no significant effect on locomotor activity and mechanical allodynia after SCI.
Baastrup C, Finnerup NB. Pharmacological management of neuropathic pain following spinal cord injury. CNS Drugs 2008;22:455-75.
Finnerup NB, Baastrup C. Spinal cord injury pain: mechanisms and management. Curr Pain Headache Rep 2012;16:207-16.
Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science 2000;288:1765-8.
Nicola NA, Metcalf D, Matsumoto M, Johnson GR. Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells. Identification as granulocyte colony-stimulating factor. J Biol Chem 1983;258:9017-23.
Roberts AW. G-CSF: a key regulator of neutrophil production, but that's not all! Growth Factors 2005;23:33-41.
Bensinger WI, Appelbaum FA, Demirer T, Torok-Storb B, Storb R, Buckner CD. Transplantation of allogeneic peripheral blood stem cells. StemCells 1995;13:63-70.
Sloand EM, Kim S, Maciejewski JP, Van Rhee F, Chaudhuri A, Barrett J, et al. Pharmacologic doses of granulocyte colonystimulating factor affect cytokine production by lymphocytes in vitro and in vivo. Blood 2000;95:2269-74.
Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 2002;3:687-94.
Möhle R, Haas R, Hunstein W. Expression of adhesion molecules and c-kit on CD34+ hematopoietic progenitor cells: comparison of cytokine-mobilized blood stem cells with normal bone marrow and peripheral blood. J Hematother 1993;2:483-9.
Ro LS, Chen SR, Chao PK, Lee YL, Lu KT. The potential application of granulocyte colony stimulating factor therapy on neuropathic pain. Chang Gung Med J 2009;32:235-46.
Rondon LJ, Privat AM, Daulhac L, Davin N, Mazur A, Fialip J, et al. Magnesium attenuates chronic hypersensitivity and spinal cord NMDA receptor phosphorylation in a rat model of diabetic neuropathic pain. J Physiol 2010;588:4205-15.
Wiseman DB, Dailey AT, Lundin D, Zhou J, Lipson A, Falicov A, et al. Magnesium efficacy in a rat spinal cord injury model. J Neurosurg Spine 2009;10:308-14.
Kauppila T. Cold exposure enhances tactile allodynia transiently in mononeuropathic rats. Exp Neurol 2000;161:740-4.
Ulugol A, Aslantas A, Ipci Y, Tuncer A, Hakan Karadag C, Dokmeci I. Combined systemic administration of morphine and magnesium sulfate attenuates pain-related behavior in mononeuropathic rats. Brain Res 2002;943:101-4.
Takaishi K, Eisele J, Carstens E. Behavioral and electrophysiological assessment of hyperalgesia and changes in dorsal horn responses following partial sciatic nerve ligation in rats. Pain 1996;66:297-306.
Yezierski RP, Green M, Murphy K, Vierck CJ. Effects of gabapentin on thermal sensitivity following spinal nerve ligation or spinal cord compression. Behav Pharmacol 2013;24:598-609.
Farsi L, NaghibZadeh M, Afshari K, Norouzi-Javidan A, Ghajarzadeh M, Naghshband Z, et al. Effects of combining methylprednisolone with magnesium sulfate on neuropathic pain and functional recovery following spinal cord injury in male rats. Acta Med Iran 2015;53:149-57.
Wallner S, Peters S, Pitzer C, Resch H, Bogdahn U, Schneider A. The Granulocyte-colony stimulating factor has a dual role in neuronal and vascular plasticity. Front Cell Dev Biol 2015;3:48.
Takahashi H, Koda M, Hashimoto M, Furuya T, Sakuma T, Kato K, et al. Transplanted Peripheral Blood Stem Cells Mobilized by Granulocyte Colony-Stimulating Factor Promoted Hindlimb Functional Recovery After Spinal Cord Injury in Mice. Cell Transplant 2016;25:283-92.
Chao P-K, Lu K-T, Lee Y-L, Chen J-C, Wang H-L, Yang Y-L, et al. Early systemic granulocyte-colony stimulating factor treatment attenuates neuropathic pain after peripheral nerve injury. PLoS One 2012;7:e43680.
Kato K, Koda M, Takahashi H, Sakuma T, Inada T, Kamiya K, et al. Granulocyte colony-stimulating factor attenuates spinal cord injury-induced mechanical allodynia in adult rats. J Neurol Neurol Sci 2015;355:79-83.
Koda M, Furuya T, Kato K, Mannoji C, Hashimoto M, Inada T, et al. Delayed granulocyte colony-stimulating factor treatment in rats attenuates mechanical allodynia induced by chronic constriction injury of the sciatic nerve. Spine 2014;39:192-7.
Xiao-Jun X, Jing-Xia H, Seiger Å, Hughes J, Hökfelt T, Wiesenfeld-Hallin Z. Chronic pain-related behaviors in spinally injured rats: Evidence for functional alterations of the endogenous cholecystokinin and opioid systems. Pain 1994;56:271-7.
Farsi L, Afshari K, Keshavarz M, NaghibZadeh M,Memari F, Norouzi-Javidan A. Postinjury treatment with magnesium sulfate attenuates neuropathic pains following spinal cord injury in male rats. Behavioural pharmacology. 2015;26:315-20.
Berrios I, Castro C, Kuffler DP. Morphine: axon regeneration, neuroprotection, neurotoxicity, tolerance, and neuropathic pain. P R Health Sci J 2008;27:119-28..
Lindsey AE, LoVerso RL, Tovar CA, Hill CE, Beattie MS, Bresnahan JC. 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;14:287-300.
Urdzíková L, Jendelová P, Glogarová K, Burian M, Hájek M, Syková E. Transplantation of bone marrow stem cells as well as mobilization by granulocyte-colony stimulating factor promotes recovery after spinal cord injury in rats. J Neurotrauma 2006;23:1379-91.
Chen WF, Chen CH, Chen NF, Sung CS, Wen ZH. Neuroprotective Effects of Direct Intrathecal Administration of Granulocyte Colony‐Stimulating Factor in Rats with Spinal Cord Injury. CNS Neurosci Therapeut 2015;21:698-707.
Carvalho TT, Borghi SM, Pinho-Ribeiro FA, Mizokami SS, Cunha TM, Ferreira SH, et al. Granulocyte-colony stimulating factor (G-CSF)induced mechanical hyperalgesia in mice: Role for peripheral TNFα, IL-1β and IL-10. Eur J Pharmacol 2015;749:62-72.
Mousa SA, Bopaiah CP, Richter JF, Yamdeu RS, Schäfer M. Inhibition of inflammatory pain by CRF at peripheral, spinal and supraspinal sites: involvement of areas coexpressing CRF receptors and opioid peptides. Neuropsychopharmacology 2007;32:2530-42.
Dale CS, Pagano RdL, Rioli V. Hemopressin: a novel bioactive peptide derived from the alpha1-chain of hemoglobin. Memórias do Instituto Oswaldo Cruz 2005;100:105-6.
Poisbeau P, Patte-Mensah C, Keller AF, Barrot M, Breton J-D, Luis-Delgado OE, et al. Inflammatory pain upregulates spinal inhibition via endogenous neurosteroid production. J Neurosci 2005;25:11768-76.
Cabot PJ, Carter L, Schäfer M, Stein C. Methionineenkephalinand Dynorphin A-release from immune cells and control of inflammatory pain. Pain 2001;93:207-12.
Mousa SA, Shakibaei M, Sitte N, Schäfer M, Stein C. Subcellular pathways of β-endorphin synthesis, processing, and release from immunocytes in inflammatory pain. Endocrinology 2004;145:1331-41.
Rittner H, Brack A, Stein C. The other side of the medal: how chemokines promote analgesia. Neurosci Lett 2008;437:203-8.
Rittner HL, Mousa SA, Labuz D, Beschmann K,SchäferM, Stein C, et al. Selective local PMN recruitment by CXCL1 or CXCL2/3 injection does not cause inflammatory pain. J Leukoc Biol 2006;79:1022-32.
Iwasaka H, Kitano T, Miyakawa H, Unoshima M, Shinguu C, Matsumoto S, et al. Neutrophilia and granulocyte colony-stimulating factor levels after cardiopulmonary bypass. Can J Anaesth 2001;48:81-4.
Brack A, Rittner HL, Stein C. Neurogenic painful inflammation. Curr Opin Anesthesiol 2004;17:461-4.
Rutella S. Granulocyte colony-stimulating factor for the induction of T-cell tolerance. Transplantation 2007;84:S26-30.
Solaroglu I, Jadhav V, Zhang JH. Neuroprotective effect of granulocyte-colony stimulating factor. Front Biosci 2007;12:e24.
Komine-Kobayashi M, Zhang N, Liu M, Tanaka R, Hara H, Osaka A, et al. Neuroprotective effect of recombinant human granulocyte colony-stimulating factor in transient focal ischemia of mice. J Cereb Blood Flow Metab 2006;26:402-13.
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