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Satellite glial cells express IL-6 and corresponding signal-transducing receptors in the dorsal root ganglia of rat neuropathic pain model

Published online by Cambridge University Press:  02 June 2010

Petr Dubový*
Affiliation:
Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Ilona Klusáková
Affiliation:
Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Ivana Svíženská
Affiliation:
Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Václav Brázda
Affiliation:
Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, Brno, Czech Republic Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic
*
Correspondence should be addressed to: Petr Dubový, Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, Kamenice 3, CZ-625 00 BrnoCzech Republic, phone: +420-5-549493701 fax: +420-5-549491323 email: pdubovy@med.muni.cz

Abstract

There is a growing body of evidence that cytokines contribute to both induction and maintenance of neuropathic pain derived from changes in dorsal root ganglia (DRG), including the activity of the primary sensory neurons and their satellite glial cells (SGC). We used immunofluorescence and in situ hybridization methods to provide evidence that chronic constriction injury (CCI) of the sciatic nerve induces synthesis of interleukin-6 (IL-6) in SGC, elevation of IL-6 receptor (IL-6R) and activation of signal transducer and activator of transcription 3 (STAT3) signalling. Unilateral CCI of the rat sciatic nerve induced mechanoallodynia and thermal hyperalgesia in ipsilateral hind paws, but contralateral paws exhibited only temporal changes of sensitivity. We demonstrated that IL-6 mRNA and protein, which were expressed at very low levels in naïve DRG, were bilaterally increased not only in L4-L5 DRG neurons but also in SGC activated by unilateral CCI. Besides IL-6, substantial increase of IL-6R and pSTAT3 expression occurred in SGC following CCI, however, IL-6R associated protein, gp130 levels did not change. The results may suggest that unilateral CCI of the sciatic nerve induces bilateral activation of SGC in L4-L5 DRG to transduce IL-6 signalling during neuroinflammation.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2010

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References

Arruda, J.L., Sweitzer, S.A., Rutkowski, M.D. and DeLeo, J.A. (2000) Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced mechanical allodynia in the rat: possible immune modulation in neuropathic pain. Brain Research 879, 216225.CrossRefGoogle ScholarPubMed
Arvidson, B. (1979) A study of the perineurial diffusion barrier of a peripheral ganglion. Acta Neuropathologica 46, 139144.CrossRefGoogle ScholarPubMed
Bennett, G.J. and Xie, Y.K. (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33, 87107.CrossRefGoogle ScholarPubMed
Brazda, V., Klusakova, I., Svizenska, I., Veselkova, Z. and Dubovy, P. (2009) Bilateral changes in IL-6 Protein, but not in its receptor gp130, in rat dorsal root ganglia following sciatic nerve ligature. Cellular and Molecular Neurobiology 29, 10531062.CrossRefGoogle Scholar
Brenn, D., Richter, F. and Schaible, H.G. (2007) Sensitization of unmyelinated sensory fibers of the joint nerve to mechanical stimuli by interleukin-6 in the rat – an inflammatory mechanism of joint pain. Arthritis and Rheumatism 56, 351359.CrossRefGoogle ScholarPubMed
Cherkas, P.S., Huang, T.Y., Pannicke, T., Tal, M., Reichenbach, A. and Hanani, M. (2004) The effects of axotomy on neurons and satellite glial cells in mouse trigeminal ganglion. Pain 110, 290298.CrossRefGoogle ScholarPubMed
Costigan, M., Scholz, J. and Woolf, C.J. (2009) Neuropathic pain: a maladaptive response of the nervous system to damage. Annual Review of Neuroscience 32, 132.CrossRefGoogle ScholarPubMed
DeLeo, J.A., Colburn, R.W., Nichols, M. and Malhotra, A. (1996) Interleukin-6-mediated hyperalgesia/allodynia and increased spinal IL-6 expression in a rat mononeuropathy model. Journal of Interferon and Cytokine Research 16, 695700.CrossRefGoogle Scholar
DeLeo, J.A. and Yezierski, R.P. (2001) The role of neuroinflammation and neuroimmune activation in persistent pain. Pain 90, 16.CrossRefGoogle ScholarPubMed
Dubovy, P., Klusakova, I. and Svizenska, I. (2002) A quantitative immunohistochemical study of the endoneurium in the rat dorsal and ventral spinal roots. Histochemistry and Cell Biology 117, 473480.CrossRefGoogle ScholarPubMed
Dubovy, P., Tuckova, L., Jancalek, R., Svizenska, I. and Klusakova, I. (2007) Increased invasion of ED-1 positive macrophages in both ipsi- and contralateral dorsal root ganglia following unilateral nerve injuries. Neuroscience Letters 427, 8893.CrossRefGoogle ScholarPubMed
Elson, K., Simmons, A. and Speck, P. (2004) Satellite cell proliferation in murine sensory ganglia in response to scarification of the skin. Glia 45, 105109.CrossRefGoogle ScholarPubMed
Gardiner, N.J., Cafferty, W.B.J., Slack, S.E. and Thompson, S.W.N. (2002) Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injury. Journal of Neurochemistry 83, 100109.CrossRefGoogle ScholarPubMed
Hama, T., Kushima, Y., Miyamoto, M., Kubota, M., Takei, N. and Hatanaka, H. (1991) Interleukin-6 improves the survival of mesencephalic catecholaminergic and septal cholinergic neurons from postnatal, 2-week-old rats in cultures. Neuroscience 40, 445452.CrossRefGoogle Scholar
Hanani, M. (2005) Satellite glial cells in sensory ganglia: from form to function. Brain Research Reviews 48, 457476.CrossRefGoogle ScholarPubMed
Harnicarova, A., Kozubek, S., Pachernik, J., Krejci, J. and Bartova, E. (2006) Distinct nuclear arrangement of active and inactive c-myc genes in control and differentiated colon carcinoma cells. Experimental Cell Research 312, 40194035.CrossRefGoogle ScholarPubMed
Heinrich, P.C., Behrmann, I., Muller-Newen, G., Schaper, F. and Graeve, L. (1998) Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochemical Journal 334, 297314.CrossRefGoogle ScholarPubMed
Hibi, M., Nakajima, K. and Hirano, T. (1996) IL-6 cytokine family and signal transduction: a model of the cytokine system. Journal of Molecular Medicine-Jmm 74, 112.CrossRefGoogle Scholar
Honore, P., Rogers, S.D., Schwei, M.J., Salak-Johnson, J.L., Luger, N.M., Sabino, M.C., Clohisy, D.R. and Mantyh, P.W. (2000) Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons. Neuroscience 98, 585598.CrossRefGoogle ScholarPubMed
Hu, P. and McLachlan, E.M. (2002) Macrophage and lymphocyte invasion of dorsal root ganglia after peripheral nerve lesions in the rat. Neuroscience 112, 2338.CrossRefGoogle ScholarPubMed
Humbertson, A., Zimmerman, E. and Leedy, M. (1969) A chronological study of mitotic activity in satellite cell hyperplasia associated with chromatolytic neurons. Zeitschrift Fur Zellforschung Und Mikroskopische Anatomie 100, 507524.CrossRefGoogle ScholarPubMed
Ikeda, K., Iwasaki, Y., Shiojima, T. and Kinoshita, M. (1996) Neuroprotective effect of various cytokines on developing spinal motoneurons following axotomy. Journal of the Neurological Sciences 135, 109113.CrossRefGoogle ScholarPubMed
Jensen, T.S., Gottrup, H., Sindrup, S.H. and Bach, F.W. (2001) The clinical picture of neuropathic pain. Spring Meeting of the European – Journal of Pharmacology 429, 111.CrossRefGoogle ScholarPubMed
Jones, S.A., Horiuchi, S., Topley, N., Yamamoto, N. and Fuller, G.M. (2001) The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB Journal 15, 4358.CrossRefGoogle ScholarPubMed
Kirita, T., Takebayashi, T., Mizuno, S., Takeuchi, H., Kobayashi, T., Fukao, M., Yamashita, T. and Tohse, N. (2007) Electrophysiologic changes in dorsal root ganglion neurons and behavioral changes in a lumbar radiculopathy model. Spine 32, E65E72.CrossRefGoogle Scholar
Kishimoto, T., Akira, S., Narazaki, M. and Taga, T. (1995) Interleukin-6 family of cytokines and gp130. Blood 86, 12431254.CrossRefGoogle ScholarPubMed
Li, C.Q., Xu, J.M., Liu, D., Zhang, J.Y. and Dai, R.P. (2008) Brain derived neurotrophic factor (BDNF) contributes to the pain hypersensitivity following surgical incision in the rats. Molecular Pain 4, 111; doi:10.1186/1744-8069-4-27CrossRefGoogle Scholar
Marz, P., Otten, U. and Rose-John, S. (1999) Neural activities of IL-6-type cytokines often depend on soluble cytokine receptors. European Journal of Neuroscience 11, 29953004.CrossRefGoogle ScholarPubMed
McMahon, S.B., Cafferty, W.B.J. and Marchand, F. (2005) Immune and glial cell factors as pain mediators and modulators. Experimental Neurology 192, 444462.CrossRefGoogle ScholarPubMed
Milligan, E.D., Twining, C., Chacur, M., Biedenkapp, J., O'Connor, K., Poole, S., Tracey, K., Martin, D., Maier, S.F. and Watkins, L.R. (2003) Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats. Journal of Neuroscience 23, 10261040.CrossRefGoogle ScholarPubMed
Murphy, P.G., Borthwick, L.S., Johnston, R.S., Kuchel, G. and Richardson, P.M. (1999) Nature of the retrograde signal from injured nerves that induces interleukin-6 mRNA in neurons. Journal of Neuroscience 19, 37913800.CrossRefGoogle ScholarPubMed
Murphy, P.G., Grondin, J., Altares, M. and Richardson, P.M. (1995) Induction of interleukin-6 in axotomized sensory neurons. Journal of Neuroscience 15, 51305138.CrossRefGoogle ScholarPubMed
Obreja, O., Biasio, W., Andratsch, M., Lips, K.S., Rathee, P.K., Ludwig, A., Rose-John, S. and Kress, M. (2005) Fast modulation of heat-activated ionic current by proinflammatory interleukin 6 in rat sensory neurons. Brain 128, 16341641.CrossRefGoogle ScholarPubMed
Obreja, O., Schmelz, M., Poole, S. and Kress, M. (2002) Interleukin-6 in combination with its soluble IL-6 receptor sensitises rat skin nociceptors to heat, in vivo. Pain 96, 5762.CrossRefGoogle ScholarPubMed
Oka, T., Oka, K., Hosoi, M. and Hori, T. (1995) Intracerebroventricular injection of interleukin-6 induces thermal hyperalgesia in rats. Brain Research 692, 123128.CrossRefGoogle ScholarPubMed
Pannese, E. (1981) The satellite cells of the sensory ganglia. Advances in Anatomy, Embryology, and Cell Biology 65, 1111.CrossRefGoogle ScholarPubMed
Qiu, J., Cafferty, W.B.J., McMahon, S.B. and Thompson, S.W.N. (2005) Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation. Journal of Neuroscience 25, 16451653.CrossRefGoogle ScholarPubMed
Ramer, M.S., Murphy, P.G., Richardson, P.M. and Bisby, M.A. (1998) Spinal nerve lesion-induced mechanoallodynia and adrenergic sprouting in sensory ganglia are attenuated in interleukin-6 knockout mice. Pain 78, 115121.CrossRefGoogle ScholarPubMed
Rose-John, S. and Heinrich, P.C. (1994) Soluble receptors for cytokines and growth-factors: generation and biological function. Biochemical Journal 300, 281290.CrossRefGoogle ScholarPubMed
Rose-John, S., Scheller, J., Elson, G. and Jones, S.A. (2006) Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. Journal of Leukocyte Biology 80, 227236.CrossRefGoogle ScholarPubMed
Ryoke, K., Ochi, M., Iwata, A., Uchio, Y., Yamamoto, S. and Yamaguchi, H. (2000) A conditioning lesion promotes in vivo nerve regeneration in the contralateral sciatic nerve of rats. Biochemical and Biophysical Research Communications 267, 715718.CrossRefGoogle ScholarPubMed
Schafers, M., Geis, C., Svensson, C.I., Luo, Z.D. and Sommer, C. (2003) Selective increase of tumour necrosis factor-alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve. European Journal of Neuroscience 17, 791804.CrossRefGoogle ScholarPubMed
Scheller, J. and Rose-John, S. (2006) Interleukin-6 and its receptor: from bench to bedside. Medical Microbiology and Immunology 195, 173183.CrossRefGoogle ScholarPubMed
Schoeniger-Skinner, D.K., Ledeboer, A., Frank, M.G., Milligan, E.D., Poole, S., Martin, D., Maier, S.F. and Watkins, L.R. (2007) Interleukin-6 mediates low-threshold mechanical allodynia induced by intrathecal HIV-1 envelope glycoprotein gp120. Brain Behavior and Immunity 21, 660667.CrossRefGoogle ScholarPubMed
Scholz, J. and Woolf, C.J. (2002) Can we conquer pain? Nature Neuroscience 5, 10621067.CrossRefGoogle ScholarPubMed
Schwaiger, F.W., Hager, G., Schmitt, A.B., Horvat, A., Streif, R., Spitzer, C., Gamal, S., Breuer, S., Brook, G.A., Nacimiento, W. and Kreutzberg, G.W. (2000) Peripheral but not central axotomy induces changes in Janus kinases (JAK) and signal transducers and activators of transcription (STAT). European Journal of Neuroscience 12, 11651176.CrossRefGoogle Scholar
Sheu, J.Y., Kulhanek, D.J. and Eckenstein, F.P. (2000) Differential patterns of ERK and STAT3 phosphorylation after sciatic nerve transection in the rat. Experimental Neurology 166, 392402.CrossRefGoogle ScholarPubMed
Sommer, C. and Kress, M. (2004) Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neuroscience Letters 361, 184187.CrossRefGoogle ScholarPubMed
Sommer, C. and Schafers, M. (1998) Painful mononeuropathy in C57BL/Wld mice with delayed Wallerian degeneration: differential effects of cytokine production and nerve regeneration on thermal and mechanical hypersensitivity. Brain Research 784, 154162.CrossRefGoogle ScholarPubMed
Sommer, C., Schmidt, C. and George, A. (1998) Hyperalgesia in experimental neuropathy is dependent on the TNF receptor 1. Experimental Neurology 151, 138142.CrossRefGoogle ScholarPubMed
Song, X.J., Zhang, J.M., Hu, S.J. and LaMotte, R.H. (2003) Somata of nerve-injured sensory neurons exhibit enhanced responses to inflammatory mediators. Pain 104, 701709.CrossRefGoogle ScholarPubMed
Taga, T. (1996) gp130, a shared signal transducing receptor component for hematopoietic and neuropoietic cytokines. Journal of Neurochemistry 67, 110.CrossRefGoogle ScholarPubMed
Takeda, M., Kitagawa, J., Takahashi, M. and Matsumoto, S. (2008a) Activation of interleukin-1 beta receptor suppresses the voltage-gated potassium currents in the small-diameter trigeminal ganglion neurons following peripheral inflammation. Pain 139, 594602.CrossRefGoogle ScholarPubMed
Takeda, M., Takahashi, M. and Matsumoto, S. (2008b) Contribution of activated interleukin receptors in trigeminal ganglion neurons to hyperalgesia via satellite glial interleukin-1 beta paracrine mechanism. Brain Behavior and Immunity 22, 10161023.CrossRefGoogle ScholarPubMed
Takeda, M., Takahashi, M. and Matsumoto, S. (2009) Contribution of the activation of satellite glia in sensory ganglia to pathological pain. Neuroscience and Biobehavioral Reviews 33, 784792.CrossRefGoogle ScholarPubMed
Takeda, M., Tanimoto, T., Kadoi, J., Nasu, M., Takahashi, M., Kitagawa, J. and Matsumoto, S. (2007) Enhanced excitability of nociceptive trigeminal ganglion neurons by satellite glial cytokine following peripheral inflammation. Pain 129, 155166.CrossRefGoogle ScholarPubMed
Vit, J.P., Ohara, P.T., Bhargava, A., Kelley, K. and Jasmin, L. (2008) Silencing the kir4.1 potassium channel subunit in satellite glial cells of the rat trigeminal ganglion results in pain-like behavior in the absence of nerve injury. Journal of Neuroscience 28, 41614171.CrossRefGoogle ScholarPubMed
Wang, H., Sun, H., Della Penna, K., Benz, R.J., Xu, J., Gerhold, D.L., Holder, D.J. and Koblan, K.S. (2002) Chronic neuropathic pain is accompanied by global changes in gene expression and shares pathobiology with neurodegenerative diseases. Neuroscience 114, 529546.CrossRefGoogle ScholarPubMed
Watkins, L.R., Hutchinson, M.R., Johnston, I.N. and Maier, S.F. (2005) Glia: novel counter-regulators of opioid analgesia. Trends in Neurosciences 28, 661669.CrossRefGoogle ScholarPubMed
Watkins, L.R., Hutchinson, M.R., Milligan, E.D. and Maier, S.F. (2007) “Listening” and “talking” to neurons: implications of immune activation for pain control and increasing the efficacy of opioids. Brain Research Reviews 56, 148169.CrossRefGoogle ScholarPubMed
Woolf, C.J. and Mannion, R.J. (1999) Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 353, 19591964.CrossRefGoogle ScholarPubMed
Woolf, C.J. and Salter, M.W. (2000) Neuroscience – neuronal plasticity: increasing the gain in pain. Science 288, 17651768.CrossRefGoogle Scholar
Xiao, H.S., Huang, Q.H., Zhang, F.X., Bao, L., Lu, Y.J., Guo, C., Yang, L., Huang, W.J., Fu, G., Xu, S.H., Cheng, X.P., Yan, Q., Zhu, Z.D., Zhang, X., Chen, Z. and Han, Z.G. (2002) Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proceedings of the National Academy of Sciences of the United States of America 99, 83608365.CrossRefGoogle ScholarPubMed
Yamaguchi, H., Ochi, M., Mori, R., Ryoke, K., Yamamoto, S., Iwata, A. and Uchio, Y. (1999) Unilateral sciatic nerve injury stimulates contralateral nerve regeneration. Neuroreport 10, 13591362.CrossRefGoogle ScholarPubMed
Zamboni, L. and DeMartino, C. (1967) Buffered picric acid-formaldehyde – a new rapid fixative for electron microscopy. Journal of Cell Biology 35, A148.Google Scholar
Zhong, J., Dietzel, I.D., Wahle, P., Kopf, M. and Heumann, R. (1999) Sensory impairments and delayed regeneration of sensory axons in interleukin-6-deficient mice. Journal of Neuroscience 19, 43054313.CrossRefGoogle ScholarPubMed
Zhou, X.F., Chie, E.T., Deng, Y.S., Zhong, J.H., Xue, Q., Rush, R.A. and Xian, C.J. (1999) Injured primary sensory neurons switch phenotype for brain-derived neurotrophic factor in the rat. Neuroscience 92, 841853.CrossRefGoogle ScholarPubMed
Zhou, X.F., Rush, R.A. and McLachlan, E.M. (1996) Differential expression of the p75 nerve growth factor receptor in glia and neurons of the rat dorsal root ganglia after peripheral nerve transection. Journal of Neuroscience 16, 29012911.CrossRefGoogle ScholarPubMed
Zimmermann, M. (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16, 109110.CrossRefGoogle ScholarPubMed
Zimmermann, M. (2001) Pathobiology of neuropathic pain. European Journal of Pharmacology 429, 2337.CrossRefGoogle ScholarPubMed