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Retrograde Cellular Changes After Nerve Injury

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Encyclopedia of Pain

Synonyms

Axotomy; Bennett model; Chung model; Gazelius model; Nerve injury; Nerve ligation; Other types of nerve injury; Seltzer model; Spared nerve injury

Definition

Retrograde changes here refer to the alteration in expression of various molecules in the parent dorsal root ganglion (DRG, sensory) or autonomic neurons after any type of lesion of the peripheral axon (branch). This occurs in humans after various types of lesions, for example, surgery, and is mimicked in experimental animal models, mainly in attempts to understand mechanisms underlying neuropathic pain.

Characteristics

Nerve Injury and Neuropathic Pain

Nerve injury, such as transection of a nerve (axotomy), occurs under a wide variety of circumstances in real life, ranging from a simple accidental cut during cooking to more or less complicated surgical procedures in hospitals, amputation of a limb being the extreme. Early work on experimental animals by Wall, Devor, and colleagues showed that such a transection has...

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References

  • Azkue, J. J., Zimmermann, M., Hsieh, T. F., et al. (1998). Peripheral nerve insult induces NMDA receptor-mediated, delayed degeneration in spinal neurons. The European Journal of Neuroscience, 10, 2204–2206.

    PubMed  CAS  Google Scholar 

  • Bao, L., Wang, H. F., Cai, H. J., et al. (2002). Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord. The European Journal of Neuroscience, 16, 175–185.

    PubMed  Google Scholar 

  • Bradman, M. J., Arora, D. K., Morris, R., et al. (2010). How do the satellite glia cells of the dorsal root ganglia respond to stressed neurons? – nitric oxide saga from embryonic development to axonal injury in adulthood. Neuron Glia Biology, 6, 11–17.

    PubMed  Google Scholar 

  • Brumovsky, P., Stanic, D., Shuster, S., et al. (2005). Neuropeptide Y2 receptor protein is present in peptidergic and nonpeptidergic primary sensory neurons of the mouse. The Journal of Comparative Neurology, 489, 328–348.

    PubMed  CAS  Google Scholar 

  • Brumovsky, P., Villar, M. J., & Hökfelt, T. (2006). Tyrosine hydroxylase is expressed in a subpopulation of small dorsal root ganglion neurons in the adult mouse. Experimental Neurology, 200, 153–165.

    PubMed  CAS  Google Scholar 

  • Brumovsky, P., Shi, T. S., Landry, M., et al. (2007a). Neuropeptide tyrosine and pain. Trends in Pharmacological Sciences, 25, 93–102.

    Google Scholar 

  • Brumovsky, P., Watanabe, M., & Hökfelt, T. (2007b). Expression of the vesicular glutamate transporters-1 and -2 in adult mouse dorsal root ganglia and spinal cord and their regulation by nerve injury. Neuroscience, 147, 469–490.

    PubMed  CAS  Google Scholar 

  • Brumovsky, P. R., Robinson, D. R., La, J. H., et al. (2011). Expression of vesicular glutamate transporters type 1 and 2 in sensory and autonomic neurons innervating the mouse colorectum. The Journal of Comparative Neurology, 519, 3346–3366.

    PubMed  CAS  Google Scholar 

  • Calvo, M., & Bennett, D. L. (2012). The mechanisms of microgliosis and pain following peripheral nerve injury. Experimental Neurology, 234, 271–282.

    PubMed  CAS  Google Scholar 

  • Coggeshall, R. E., Lekan, H. A., White, F. A., et al. (2001). A-fiber sensory input induces neuronal cell death in the dorsal horn of the adult rat spinal cord. The Journal of Comparative Neurology, 435, 276–282.

    PubMed  CAS  Google Scholar 

  • Costigan, M., Befort, K., Karchewski, L., et al. (2002). Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neuroscience, 3, 16.

    PubMed  Google Scholar 

  • Devor, M., & Wall, P. D. (1981). Plasticity in the spinal cord sensory map following peripheral nerve injury in rats. The Journal of Neuroscience, 1, 679–684.

    PubMed  CAS  Google Scholar 

  • Dib-Hajj, S. D., Cummins, T. R., Black, J. A., et al. (2010). Sodium channels in normal and pathological pain. Annual Review of Neuroscience, 33, 325–347.

    PubMed  CAS  Google Scholar 

  • Djuranovic, S., Nahvi, A., & Green, R. (2011). A parsimonious model for gene regulation by miRNAs. Science, 331, 550–553.

    PubMed  CAS  Google Scholar 

  • Dubner, R., & Ruda, M. A. (1992). Activity-dependent neuronal plasticity following tissue injury and inflammation. Trends in Neurosciences, 15, 96–103.

    PubMed  CAS  Google Scholar 

  • Ernsberger, U. (2009). Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia. Cell and Tissue Research, 336, 349–384.

    PubMed  CAS  Google Scholar 

  • Gardell, L. R., Wang, R., Ehrenfels, C., et al. (2003). Multiple actions of systemic artemin in experimental neuropathy. Nature Medicine, 9, 1383–1389.

    PubMed  CAS  Google Scholar 

  • Gibbs, G. F., Drummond, P. D., Finch, P. M., et al. (2008). Unravelling the pathophysiology of complex regional pain syndrome: Focus on sympathetically maintained pain. Clinical and Experimental Pharmacology & Physiology, 35, 717–724.

    CAS  Google Scholar 

  • Grothe, C., Meisinger, C., & Claus, P. (2001). In vivo expression and localization of the fibroblast growth factor system in the intact and lesioned rat peripheral nerve and spinal ganglia. The Journal of Comparative Neurology, 434, 342–357.

    PubMed  CAS  Google Scholar 

  • Hobson, S. A., Bacon, A., Elliot-Hunt, C. R., et al. (2008). Galanin acts as a trophic factor to the central and peripheral nervous systems. Cellular and Molecular Life Sciences, 65, 1806–1812.

    PubMed  CAS  Google Scholar 

  • Hökfelt, T., Zhang, X., & Wiesenfeld-Hallin, Z. (1994). Messenger plasticity in primary sensory neurons following axotomy and its functional implications. Trends in Neurosciences, 17, 22–30.

    Google Scholar 

  • Hökfelt, T., Zhang, X., Xu, Z.-Q., et al. (1997). Cellular and synaptic mechanisms in transition of pain from acute to chronic. In T. S. Jensen, J. A. Turner, & Z. Wiesenfeld-Hallin (Eds.), Proceedings of the 8th World CongrPain, Prog Pain Res Management, vol 8 (pp. 133–153). Seattle: IASP Press.

    Google Scholar 

  • Hökfelt, T., Zhang, X., Xu, X. J., & Wiesenfeld-Hallin, Z. S. (2005). Central consequences of peripheral nerve damage (Chapter 60). In S. McMahon & M. Koltzenburg (Eds.), Textbook of pain (5th ed., pp. 947–959). Churchill Livingstone: Elsevier.

    Google Scholar 

  • Jänig, W. (2003). Relationship between pain and autonomic phenomena in headache and other pain conditions. Cephalalgia, 23(Suppl 1), 43–48.

    PubMed  Google Scholar 

  • Koltzenburg, M. (2005). Mechanisms of peripheral neuropathic pain. In S. Hunt & M. Koltzenburg (Eds.), The neurobiology of pain (pp. 115–147). Oxford: Oxford University Press.

    Google Scholar 

  • Kullman, D. M., & Waxman, S. G. (2010). Neurological channelopathies: New insights into disease mechanisms and ion channel function. The Journal of Physiology, 588, 1823–1827.

    Google Scholar 

  • Kusuda, R., Cadetti, F., Ravanelli, M. I., Sousa, T. A., Zanon, S., De Lucca, F. L., & Lucas, G. (2011). Differential expression of microRNAs in mouse pain models. Molecular Pain, 7, 17.

    PubMed  CAS  Google Scholar 

  • Lallemend, F., & Ernfors, P. (2012). Molecular interactions underlying the specification of sensory neurons. Trends in Neurosciences, 35, 373–381.

    PubMed  CAS  Google Scholar 

  • Landry, M., Holmberg, K., Zhang, X., & Hökfelt, T. (2000). Effect of axotomy on expression of NPY, galanin, and NPY Y1 and Y2 receptors in dorsal root ganglia and the superior cervical ganglion studied with double-labeling in situ hybridization and immunohistochemistry. Experimental Neurology, 162, 361–384.

    PubMed  CAS  Google Scholar 

  • Landry, M., Aman, K., Dostrovsky, J., et al. (2003). Galanin expression in adult human dorsal root ganglion neurons. Neuroscience, 117, 795–809.

    PubMed  CAS  Google Scholar 

  • Lauria, G., Morbin, M., & Lombardi, R. (2006). Expression of capsaicin receptor immunoreactivity in human peripheral nervous system and in painful neuropathies. Journal of the Peripheral Nervous System, 11, 262–271.

    PubMed  CAS  Google Scholar 

  • Lee, J. W., Siegel, S. M., & Oaklander, A. L. (2009). Effects of distal nerve injuries on dorsal-horn neurons and glia: Relationships between lesion size and mechanical hyperalgesia. Neuroscience, 158, 904–914.

    PubMed  CAS  Google Scholar 

  • Lindh, B., Risling, M., Remahl, S., et al. (1993). Peptide-immunoreactive neurons and nerve fibres in lumbosacral sympathetic ganglia: Selective elimination of a pathway-specific expression of immunoreactivities following sciatic nerve resection in kittens. Neuroscience, 55, 545–562.

    PubMed  CAS  Google Scholar 

  • McGraw, J., Gaudet, A. D., Oschipok, L. W., et al. (2005). Regulation of neuronal and glial galectin-1 expression by peripheral and central axotomy of rat primary afferent neurons. Experimental Neurology, 195, 103–114.

    PubMed  CAS  Google Scholar 

  • McMahon, S. B., & Priestley, J. V. (2005). Nociceptor plasticity. In S. P. Hunt & M. Koltzenburg (Eds.), The neurobiology of pain (pp. 35–64). Oxford: OUP.

    Google Scholar 

  • Miller, K. E., Hoffman, E. M., Sutharshan, M., et al. (2011). Glutamate pharmacology and metabolism in peripheral primary afferents: Physiological and pathophysiological mechanisms. Pharmacology & Therapeutics, 130, 283–309.

    CAS  Google Scholar 

  • Mogil, J. S. (2012). Pain genetics: Past, present and future. Trends in Genetics, 28, 258–266.

    PubMed  CAS  Google Scholar 

  • Navarro, X. (2009). Chapter 27: Neural plasticity after nerve injury and regeneration. International Review of Neurobiology, 87, 483–505.

    PubMed  Google Scholar 

  • Obata, K., & Noguchi, K. (2006). BDNF in sensory neurons and chronic pain. Neuroscience Research, 55, 1–10.

    PubMed  CAS  Google Scholar 

  • O’Callaghan, J. P., & Miller, D. B. (2010). Spinal glia and chronic pain. Metabolism, 59(Suppl 1), S21–S26.

    PubMed  Google Scholar 

  • Persson, A. K., Xu, X. J., Wiesenfeld-Hallin, Z., et al. (2010). Expression of DRG candidate pain molecules after nerve injury – a comparative study among five inbred mouse strains with contrasting pain phenotypes. Journal of the Peripheral Nervous System, 15, 26–39.

    PubMed  CAS  Google Scholar 

  • Przewłocki, R., & Przewłocki, B. (2001). Opioids in chronic pain. European Journal of Pharmacology, 429, 79–91.

    PubMed  Google Scholar 

  • Raab, M., & Neuhuber, W. L. (2007). Glutamatergic functions of primary afferent neurons with special emphasis on vagal afferents. International Review of Cytology, 256, 223–275.

    PubMed  CAS  Google Scholar 

  • Rabert, D., Xiao, Y., Yiangou, Y., et al. (2004). Plasticity of gene expression in injured human dorsal root ganglia revealed by GeneChip oligonucleotide microarrays. Journal of Clinical Neuroscience, 2004(11), 289–299.

    Google Scholar 

  • Rao, M. S., Sun, Y., Escary, J. L., et al. (1993). Leukemia inhibitory factor mediates an injury response but not a target-directed developmental transmitter switch in sympathetic neurons. Neuron, 11, 1175–1185.

    PubMed  CAS  Google Scholar 

  • Salter, M. W. (2005). Cellular signalling pathways of spinal pain neuroplasticity as targets for analgesic development. Current Topics in Medicinal Chemistry, 5, 557–567.

    PubMed  CAS  Google Scholar 

  • Scholz, J., & Woolf, C. (2005). Mechanisms of neuropathic pain. In P. Marco (Ed.), The neurological basis of pain (pp. 71–95). New York: McGraw-Hill.

    Google Scholar 

  • Seal, R. P., Wang, X., Guan, Y., et al. (2009). Injury-induced mechanical hypersensitivity requires C-low threshold mechanoreceptors. Nature, 462, 651–655.

    PubMed  CAS  Google Scholar 

  • Shi, T. J., Tandrup, T., Bergman, E., et al. (2001). Effect of peripheral nerve injury on dorsal root ganglion neurons in the C57 BL/6J mouse: Marked changes both in cell numbers and neuropeptide expression. Neuroscience, 105, 249–263.

    PubMed  CAS  Google Scholar 

  • Smith, P. A., Moran, T. D., Abdulla, F., et al. (2007). Spinal mechanisms of NPY analgesia. Peptides, 28, 464–474.

    PubMed  CAS  Google Scholar 

  • Takeuchi, H., Kawaguchi, S., Mizuno, S., et al. (2008). Gene expression profile of dorsal root ganglion in a lumbar radiculopathy model. Spine, 33, 2483–2488.

    PubMed  Google Scholar 

  • Tal, M., Wall, P. D., & Devor, M. (1999). Myelinated afferent fiber types that become spontaneously active and mechanosensitive following nerve transection in the rat. Brain Research, 824, 218–223.

    PubMed  CAS  Google Scholar 

  • Tandrup, T. (2004). Unbiased estimates of number and size of rat dorsal root ganglion cells in studies of structure and cell survival. Journal of Neurocytology, 33, 173–192.

    PubMed  Google Scholar 

  • Watkins, L. R., Hutchinson, M. R., Milligan, E. D., et al. (2007). “Listening” and “talking” to neurons: Implications of immune activation for pain control and increasing the efficacy of opioids. Brain Research Reviews, 56, 148–169.

    PubMed  CAS  Google Scholar 

  • Welin, D., Novikova, L. N., Wiberg, M., et al. (2008). Survival and regeneration of cutaneous and muscular afferent neurons after peripheral nerve injury in adult rats. Experimental Brain Research, 186, 315–323.

    Google Scholar 

  • Woolf, C. J., Shortland, P., & Coggeshall, R. E. (1992). Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature, 355, 75–78.

    PubMed  CAS  Google Scholar 

  • Wynick, D., Thompson, S. W., & McMahon, S. B. (2001). The role of galanin as a multi-functional neuropeptide in the nervous system. Current Opinion in Pharmacology, 1, 73–77.

    PubMed  CAS  Google Scholar 

  • Xiao, H. S., Huang, Q. H., Zhang, F. X., et al. (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, 8360–8365.

    PubMed  CAS  Google Scholar 

  • Xu, X. J., Hökfelt, T., & Wiesenfeld-Hallin, Z. (2008). Galanin and spinal pain mechanisms: Where do we stand in 2008? Cellular and Molecular Life Sciences, 65, 1813.

    PubMed  CAS  Google Scholar 

  • Yang, L., Zhang, F. X., Huang, F., et al. (2004). Peripheral nerve injury induces trans-synaptic modification of channels, receptors and signal pathways in rat dorsal spinal cord. The European Journal of Neuroscience, 19, 871–883.

    PubMed  Google Scholar 

  • Zhang, X., Ju, G., Elde, R., et al. (1993). Effect of peripheral nerve cut on neuropeptides in dorsal root ganglia and the spinal cord of monkey with special reference to galanin. Journal of Neurocytology, 22, 342–381.

    PubMed  CAS  Google Scholar 

  • Zhou, S., Yu, B., Qian, T., Yao, D., et al. (2011). Early changes of microRNAs expression in the dorsal root ganglia following rat sciatic nerve transection. Neuroscience Letters, 494, 89–93.

    PubMed  CAS  Google Scholar 

  • Zhuo, M., Wu, G., & Wu, L. J. (2011). Neuronal and microglial mechanisms of neuropathic pain. Molecular Brain, 4, 31.

    PubMed  CAS  Google Scholar 

  • Zigmond, R. E., & Sun, Y. (1997). Regulation of neuropeptide expression in sympathetic neurons. Paracrine and retrograde influences. Annals of the New York Academy of Sciences, 814, 181–197.

    PubMed  CAS  Google Scholar 

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Acknowledgement

This work was supported by the Swedish Research Council, the Marianne and Marcus Wallenberg Foundation, the Knut and Alice Wallenberg Foundation, funds from Karolinska Institutet, the International Association for the Study of Pain, an Unrestricted Bristol-Myers Squibb Neuroscience Grant, CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), and the Austral University. We thank Drs. Zsuzsanna Wiesenfeld-Hallin, Xiao-Jun Xu, and Zhang Xu for valuable support.

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Brumovsky, P., Villar, M., Hökfelt, T. (2013). Retrograde Cellular Changes After Nerve Injury. In: Gebhart, G.F., Schmidt, R.F. (eds) Encyclopedia of Pain. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28753-4_3823

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