Granulocyte colony stimulating factor (GCSF) treatment in neuropathic pain
Abstract
Granulocyte colony stimulating factor (GCSF) is an endogenous growth factor that can stimulate granulocyte formation and is used widely in hematogenous disease without significant clinical side effects. Several clinical and animal studies had showed that both a single high-dose and repeated low-dose systemic GCSF treatment can attenuate neuropathic pain after central or peripheral nerve injury. GCSF treatment can recruit more opioid containing neutrophils to injured tissue, up-regulate opioid receptors (mu opioid receptor) on the injured nerve, which decreased nociceptive signals from injured nerve to the spinal dorsal horn. Thereafter, activated microglia, increased phosphorylated-p38 (p-p38) and pro-inflammatory cytokines on the spinal dorsal horn are suppressed, which further attenuated neuropathic pain. The systemic GCSF administration may avoid the addiction side effect induced by repeated exogenous opioid exposure and provide a new therapeutic strategy to treat neuropathic pain.
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Anderlini, P., Przepiorka, D., Champlin, R., & Korbling, M. (1996). Biologic and clinical effects of granulocyte colony-stimulating factor in normal individuals. Blood, 88(8), 2819-2825.
Apfel, C., Banner, D. W., Bur, D., Dietz, M., Hubschwerlen, C., Locher, H., . . . Stalder, H. (2001). 2-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)- and 2-(2,2-dioxo-1,4-dihydro-2H-2lambda6-benzo[1,2,6]thiadiazin-3-yl)-N-hydroxy-aceta mides as potent and selective peptide deformylase inhibitors. J Med Chem, 44(12), 1847-1852.
Avalos, B. R. (1996). Molecular analysis of the granulocyte colony-stimulating factor receptor. Blood, 88(3), 761-777.
Basbaum, A. I., Bautista, D. M., Scherrer, G., & Julius, D. (2009). Cellular and molecular mechanisms of pain. Cell, 139(2), 267-284. doi:10.1016/j.cell.2009.09.028
Bonica, J. J. (1979). The need of a taxonomy. Pain, 6(3), 247-248.
Carvalho, T. T., Flauzino, T., Otaguiri, E. S., Batistela, A. P., Zarpelon, A. C., Cunha, T. M., . . . Verri, W. A., Jr. (2011). Granulocyte-colony stimulating factor (G-CSF) induces mechanical hyperalgesia via spinal activation of MAP kinases and PI3K in mice. Pharmacol Biochem Behav, 98(2), 188-195. doi:10.1016/j.pbb.2010.12.027
Chao, P. K., Lu, K. T., Lee, Y. L., Chen, J. C., Wang, H. L., Yang, Y. L., . . . Ro, L. S. (2012). Early systemic granulocyte-colony stimulating factor treatment attenuates neuropathic pain after peripheral nerve injury. PLoS One, 7(8), e43680. doi:10.1371/journal.pone.0043680
Chen, W. F., Jean, Y. H., Sung, C. S., Wu, G. J., Huang, S. Y., Ho, J. T., . . . Wen, Z. H. (2008). Intrathecally injected granulocyte colony-stimulating factor produced neuroprotective effects in spinal cord ischemia via the mitogen-activated protein kinase and Akt pathways. Neuroscience, 153(1), 31-43. doi:10.1016/j.neuroscience.2008.01.062
Chiu, I. M., von Hehn, C. A., & Woolf, C. J. (2012). Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology. Nat Neurosci, 15(8), 1063-1067. doi:10.1038/nn.3144
Coggeshall, R. E., Zhou, S., & Carlton, S. M. (1997). Opioid receptors on peripheral sensory axons. Brain Res, 764(1-2), 126-132.
Demetri, G. D., & Griffin, J. D. (1991). Granulocyte colony-stimulating factor and its receptor. Blood, 78(11), 2791-2808.
Floel, A., Warnecke, T., Duning, T., Lating, Y., Uhlenbrock, J., Schneider, A., . . . Schabitz, W. R. (2011). Granulocyte-colony stimulating factor (G-CSF) in stroke patients with concomitant vascular disease--a randomized controlled trial. PLoS One, 6(5), e19767. doi:10.1371/journal.pone.0019767
Guo, Y., Zhang, H., Yang, J., Liu, S., Bing, L., Gao, J., & Hao, A. (2013). Granulocyte colony-stimulating factor improves alternative activation of microglia under microenvironment of spinal cord injury. Neuroscience, 238, 1-10. doi:10.1016/j.neuroscience.2013.01.047
Hartung, T. (1998). Anti-inflammatory effects of granulocyte colony-stimulating factor. Curr Opin Hematol, 5(3), 221-225.
Heinke, B., Gingl, E., & Sandkuhler, J. (2011). Multiple targets of mu-opioid receptor-mediated presynaptic inhibition at primary afferent Adelta- and C-fibers. J Neurosci, 31(4), 1313-1322. doi:10.1523/JNEUROSCI.4060-10.2011
Inoue, K., & Tsuda, M. (2009). Microglia and neuropathic pain. Glia, 57(14), 1469-1479. doi:10.1002/glia.20871
Ji, R. R., & Suter, M. R. (2007). p38 MAPK, microglial signaling, and neuropathic pain. Mol Pain, 3, 33. doi:10.1186/1744-8069-3-33
Jin, S. X., Zhuang, Z. Y., Woolf, C. J., & Ji, R. R. (2003). p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. J Neurosci, 23(10), 4017-4022.
Kadota, R., Koda, M., Kawabe, J., Hashimoto, M., Nishio, Y., Mannoji, C., . . . Yamazaki, M. (2012). Granulocyte colony-stimulating factor (G-CSF) protects oligodendrocyte and promotes hindlimb functional recovery after spinal cord injury in rats. PLoS One, 7(11), e50391. doi:10.1371/journal.pone.0050391
Kato, K., Koda, M., Takahashi, H., Sakuma, T., Inada, T., Kamiya, K., . . . Furuya, T. (2015). Granulocyte colony-stimulating factor attenuates spinal cord injury-induced mechanical allodynia in adult rats. J Neurol Sci, 355(1-2), 79-83. doi:10.1016/j.jns.2015.05.024
Kato, K., Yamazaki, M., Okawa, A., Furuya, T., Sakuma, T., Takahashi, H., . . . Koda, M. (2013). Intravenous administration of granulocyte colony-stimulating factor for treating neuropathic pain associated with compression myelopathy: a phase I and IIa clinical trial. Eur Spine J, 22(1), 197-204. doi:10.1007/s00586-012-2556-9
Koda, M., Furuya, T., Kato, K., Mannoji, C., Hashimoto, M., Inada, T., . . . Yamazaki, M. (2014). Delayed granulocyte colony-stimulating factor treatment in rats attenuates mechanical allodynia induced by chronic constriction injury of the sciatic nerve. Spine (Phila Pa 1976), 39(3), 192-197. doi:10.1097/BRS.0000000000000108
Labuz, D., Schmidt, Y., Schreiter, A., Rittner, H. L., Mousa, S. A., & Machelska, H. (2009). Immune cell-derived opioids protect against neuropathic pain in mice. J Clin Invest, 119(2), 278-286. doi:10.1172/JCI36246
Lee, K. A., Park, K. T., Yu, H. M., Jin, H. Y., Baek, H. S., & Park, T. S. (2013). Effect of granulocyte colony-stimulating factor on the peripheral nerves in streptozotocin-induced diabetic rat. Diabetes Metab J, 37(4), 286-290. doi:10.4093/dmj.2013.37.4.286
Lee, K. M., Jeon, S. M., & Cho, H. J. (2010). Interleukin-6 induces microglial CX3CR1 expression in the spinal cord after peripheral nerve injury through the activation of p38 MAPK. Eur J Pain, 14(7), 682 e681-612. doi:10.1016/j.ejpain.2009.10.017
Lesniak, A., & Lipkowski, A. W. (2011). Opioid peptides in peripheral pain control. Acta Neurobiol Exp (Wars), 71(1), 129-138.
Li, J. L., Ding, Y. Q., Li, Y. Q., Li, J. S., Nomura, S., Kaneko, T., & Mizuno, N. (1998). Immunocytochemical localization of mu-opioid receptor in primary afferent neurons containing substance P or calcitonin gene-related peptide. A light and electron microscope study in the rat. Brain Res, 794(2), 347-352.
Liao, M. F., Yeh, S. R., Lo, A. L., Chao, P. K., Lee, Y. L., Hung, Y. H., . . . Ro, L. S. (2016). An early granulocyte colony-stimulating factor treatment attenuates neuropathic pain through activation of mu opioid receptors on the injured nerve. Sci Rep, 6, 25490. doi:10.1038/srep25490
Liou, J. T., Lui, P. W., Liu, F. C., Lai, Y. S., & Day, Y. J. (2011). Exogenous granulocyte colony-stimulating factor exacerbate pain-related behaviors after peripheral nerve injury. J Neuroimmunol, 232(1-2), 83-93. doi:10.1016/j.jneuroim.2010.10.014
Millan, M. J. (2002). Descending control of pain. Prog Neurobiol, 66(6), 355-474.
Pajkrt, D., Manten, A., van der Poll, T., Tiel-van Buul, M. M., Jansen, J., Wouter ten Cate, J., & van Deventer, S. J. (1997). Modulation of cytokine release and neutrophil function by granulocyte colony-stimulating factor during endotoxemia in humans. Blood, 90(4), 1415-1424.
Pollmacher, T., Korth, C., Mullington, J., Schreiber, W., Sauer, J., Vedder, H., . . . Holsboer, F. (1996). Effects of granulocyte colony-stimulating factor on plasma cytokine and cytokine receptor levels and on the in vivo host response to endotoxin in healthy men. Blood, 87(3), 900-905.
Pollmacher, T., Korth, C., Schreiber, W., Hermann, D., & Mullington, J. (1996). Effects of repeated administration of granulocyte colony-stimulating factor (G-CSF) on neutrophil counts, plasma cytokine, and cytokine receptor levels. Cytokine, 8(10), 799-803. doi:10.1006/cyto.1996.0106
Porreca, F., Ossipov, M. H., & Gebhart, G. F. (2002). Chronic pain and medullary descending facilitation. Trends Neurosci, 25(6), 319-325.
Rausch, O., & Marshall, C. J. (1999). Cooperation of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways during granulocyte colony-stimulating factor-induced hemopoietic cell proliferation. J Biol Chem, 274(7), 4096-4105.
Sakuma, T., Yamazaki, M., Okawa, A., Takahashi, H., Kato, K., Hashimoto, M., . . . Koda, M. (2012). Neuroprotective therapy using granulocyte colony-stimulating factor for patients with worsening symptoms of compression myelopathy, Part 1: a phase I and IIa clinical trial. Eur Spine J, 21(3), 482-489. doi:10.1007/s00586-011-2020-2
Sanchez-Ramos, J., Song, S., Sava, V., Catlow, B., Lin, X., Mori, T., . . . Arendash, G. W. (2009). Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer's mice. Neuroscience, 163(1), 55-72. doi:10.1016/j.neuroscience.2009.05.071
Scherrer, G., Imamachi, N., Cao, Y. Q., Contet, C., Mennicken, F., O'Donnell, D., . . . Basbaum, A. I. (2009). Dissociation of the opioid receptor mechanisms that control mechanical and heat pain. Cell, 137(6), 1148-1159. doi:10.1016/j.cell.2009.04.019
Schmidt, Y., Gaveriaux-Ruff, C., & Machelska, H. (2013). mu-Opioid receptor antibody reveals tissue-dependent specific staining and increased neuronal mu-receptor immunoreactivity at the injured nerve trunk in mice. PLoS One, 8(11), e79099. doi:10.1371/journal.pone.0079099
Schneider, A., Kuhn, H. G., & Schabitz, W. R. (2005). A role for G-CSF (granulocyte-colony stimulating factor) in the central nervous system. Cell Cycle, 4(12), 1753-1757. doi:10.4161/cc.4.12.2213
Song, S., Sava, V., Rowe, A., Li, K., Cao, C., Mori, T., & Sanchez-Ramos, J. (2011). Granulocyte-colony stimulating factor (G-CSF) enhances recovery in mouse model of Parkinson's disease. Neurosci Lett, 487(2), 153-157. doi:10.1016/j.neulet.2010.10.012
Stein, C., & Lang, L. J. (2009). Peripheral mechanisms of opioid analgesia. Curr Opin Pharmacol, 9(1), 3-8. doi:10.1016/j.coph.2008.12.009
Stein, C., Schafer, M., & Machelska, H. (2003). Attacking pain at its source: new perspectives on opioids. Nat Med, 9(8), 1003-1008. doi:10.1038/nm908
Truong, W., Cheng, C., Xu, Q. G., Li, X. Q., & Zochodne, D. W. (2003). Mu opioid receptors and analgesia at the site of a peripheral nerve injury. Ann Neurol, 53(3), 366-375. doi:10.1002/ana.10465
Tsuda, M., Beggs, S., Salter, M. W., & Inoue, K. (2013). Microglia and intractable chronic pain. Glia, 61(1), 55-61. doi:10.1002/glia.22379
Tsuda, M., Shigemoto-Mogami, Y., Koizumi, S., Mizokoshi, A., Kohsaka, S., Salter, M. W., & Inoue, K. (2003). P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature, 424(6950), 778-783. doi:10.1038/nature01786
Wen, Y. R., Suter, M. R., Ji, R. R., Yeh, G. C., Wu, Y. S., Wang, K. C., . . . Wang, C. C. (2009). Activation of p38 mitogen-activated protein kinase in spinal microglia contributes to incision-induced mechanical allodynia. Anesthesiology, 110(1), 155-165. doi:10.1097/ALN.0b013e318190bc16
Woolf, C. J., American College of, P., & American Physiological, S. (2004). Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med, 140(6), 441-451.
Woolf, C. J., & Mannion, R. J. (1999). Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet, 353(9168), 1959-1964. doi:10.1016/S0140-6736(99)01307-0
Xiao, B. G., Lu, C. Z., & Link, H. (2007). Cell biology and clinical promise of G-CSF: immunomodulation and neuroprotection. J Cell Mol Med, 11(6), 1272-1290. doi:10.1111/j.1582-4934.2007.00101.x
Yamazaki, M., Sakuma, T., Kato, K., Furuya, T., & Koda, M. (2013). Granulocyte colony-stimulating factor reduced neuropathic pain associated with thoracic compression myelopathy: report of two cases. J Spinal Cord Med, 36(1), 40-43. doi:10.1179/2045772312Y.0000000023
Zhao, L. R., Navalitloha, Y., Singhal, S., Mehta, J., Piao, C. S., Guo, W. P., . . . Groothuis, D. R. (2007). Hematopoietic growth factors pass through the blood-brain barrier in intact rats. Exp Neurol, 204(2), 569-573. doi:10.1016/j.expneurol.2006.12.001
DOI: http://dx.doi.org/10.18103/imr.v2i11.282
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