Regeneration of Primary Sensory Neurons

Primary sensory neurons have an inherent capacity for regeneration of their cut, crushed, or chemically lesioned axons. This capacity is displayed to a much greater extent after lesions of the peripheral axons than after lesions of their centrally directed axons. Additionally, the surrounding tissue determines to a significant extent the degree of recovery: whereas the peripheral nerve tissue provides neurotrophic support and a favorable environment for axonal growth, the central terminals of primary sensory neurons face a non-permissive and inhibitory glial tissue. Mechanical lesions of the peripheral axons of dorsal root ganglion (DRG) sensory neurons can be repaired by the intrinsic regenerative capacity of the neuron itself, when outgrowing axons from the proximal stump are able to transverse the tissue scar and reach the distal stump of the nerve. Bridging the gap with an autologous nerve graft or a short artificial graft filled with nerve growth factor (NGF) can improve recovery. Neurotoxic lesions of the axon terminals are effectively recovered by intermittent local or systemic NGF injections. A recovery from a diabetic sensory neuropathy probably requires the continuous delivery of NGF or additional neurotrophic factors. A recovery from a dorsal rhizotomy or from a dorsal column lesion can possibly be achieved by the concomitant transgene-mediated overexpression of neurotrophins, the transformation of the DRG neuron cells to a competence for regrowth, and the counteraction of the growth-inhibitory nature of the central nervous system tissue.

[1]  T. Hökfelt,et al.  Messenger plasticity in primary sensory neurons following axotomy and its functional implications , 1994, Trends in Neurosciences.

[2]  S. Ichinose,et al.  A study of induction of nerve regeneration using bioabsorbable tubes. , 2001, Journal of reconstructive microsurgery.

[3]  P. Holzer.  Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. , 1991, Pharmacological reviews.

[4]  M. Greenberg,et al.  Intracellular signaling pathways activated by neurotrophic factors. , 1996, Annual review of neuroscience.

[5]  D. Ginty,et al.  Retrograde neurotrophin signaling: Trk-ing along the axon , 2002, Current Opinion in Neurobiology.

[6]  A. Hirata,et al.  Intrathecal administration of nerve growth factor delays GAP 43 expression and early phase regeneration of adult rat peripheral nerve , 2002, Brain Research.

[7]  C. Woolf,et al.  Intrinsic versus extrinsic factors in determining the regeneration of the central processes of rat dorsal root ganglion neurons: The influence of a peripheral nerve graft , 1996, The Journal of comparative neurology.

[8]  S. McMahon,et al.  Functional regeneration of sensory axons into the adult spinal cord , 2000, Nature.

[9]  A. Basbaum,et al.  Regeneration of Sensory Axons within the Injured Spinal Cord Induced by Intraganglionic cAMP Elevation , 2002, Neuron.

[10]  P. Dijkhuizen,et al.  NT‐3 delivered by an adenoviral vector induces injured dorsal root axons to regenerate into the spinal cord of adult rats , 1998, Journal of neuroscience research.

[11]  M. Haneda,et al.  Impaired regeneration and no amelioration with aldose reductase inhibitor in crushed unmyelinated nerve fibers of diabetic rats. , 1999, Neuroreport.

[12]  M. Schwab,et al.  Long-Lasting Sprouting and Gene Expression Changes Induced by the Monoclonal Antibody IN-1 in the Adult Spinal Cord , 2002, The Journal of Neuroscience.

[13]  C. Hock,et al.  Axonal Transport of Endogenous Nerve Growth Factor (NGF) and NGF Receptor in Experimental Diabetic Neuropathy , 1994, Experimental Neurology.

[14]  G. Kreutzberg,et al.  NGF receptor-mediated reduction in axonal NGF uptake and retrograde transport following sciatic nerve injury and during regeneration , 1991, Neuron.

[15]  I. Fischer,et al.  Phosphorylated MAP1B is induced in central sprouting of primary afferents in response to peripheral injury but not in response to rhizotomy , 2002, The European journal of neuroscience.

[16]  Guido Stoll,et al.  Nerve Injury, Axonal Degeneration and Neural Regeneration: Basic Insights , 1999, Brain pathology.

[17]  R. Rush,et al.  Satellite‐cell‐derived nerve growth factor and neurotrophin‐3 are involved in noradrenergic sprouting in the dorsal root ganglia following peripheral nerve injury in the rat , 1999, The European journal of neuroscience.

[18]  S. Snyder,et al.  Neural actions of immunophilin ligands. , 1998, Trends in pharmacological sciences.

[19]  M. Holmes,et al.  Evidence that endogenous beta nerve growth factor is responsible for the collateral sprouting, but not the regeneration, of nociceptive axons in adult rats. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[20]  J. Chung,et al.  Expression of neurotrophin mRNAs in the dorsal root ganglion after spinal nerve injury. , 1999, Brain research. Molecular brain research.

[21]  P. Emson,et al.  Differential expression of growth-associated protein (GAP-43) mRNA in rat primary sensory neurons after peripheral nerve lesion: a non-radioactive in situ hybridisation study , 1992, Brain Research.

[22]  I. Darian‐Smith,et al.  Somatic sensation. , 1969, Annual review of physiology.

[23]  J. Riggs.  Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. , 1998, Neurology.

[24]  P. Distefano,et al.  Neuronal Injury Increases Retrograde Axonal Transport of the Neurotrophins to Spinal Sensory Neurons and Motor Neurons via Multiple Receptor Mechanisms , 1998, Molecular and Cellular Neuroscience.

[25]  J. Donnerer,et al.  Effect of FK506 on Neurotransmitter Content and Expression of GAP-43 in Neurotoxin-Lesioned Peripheral Sensory and Sympathetic Neurons , 2002, Pharmacology.

[26]  V. Verge,et al.  Neurotrophins and nerve injury in the adult. , 1996, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[27]  G. Terenghi,et al.  Peripheral nerve regeneration and neurotrophic factors , 1999, Journal of anatomy.

[28]  S. Strittmatter,et al.  Nogo-66 receptor antagonist peptide promotes axonal regeneration , 2002, Nature.

[29]  I. Fischer,et al.  Induction of microtubule-associated protein 1B expression in Schwann cells during nerve regeneration , 1999, Brain Research.

[30]  M. Meyer,et al.  Control of Local NGF mRNA Synthesis by Preformed Factors Rapidly Released from Peripheral Nerves , 2002, Molecular and Cellular Neuroscience.

[31]  P. Greengard,et al.  Nerve growth factor controls GAP-43 mRNA stability via the phosphoprotein ARPP-19 , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[32]  A. Vinik,et al.  Streptozotocin-Induced Diabetes Mellitus Causes Changes in Primary Sensory Neuronal Cytoskeletal mRNA Levels That Mimic Those Caused by Axotomy , 1998, Experimental Neurology.

[33]  R. Schicho,et al.  Regenerative effect of human recombinant NGF on capsaicin-lesioned sensory neurons in the adult rat , 1999, Brain Research.

[34]  D. Ceballos,et al.  Influence of aging on peripheral nerve function and regeneration , 2000, Journal of the peripheral nervous system : JPNS.

[35]  R. Hellweg,et al.  Endogenous levels of nerve growth factor (NGF) are altered in experimental diabetes mellitus: A possible role for NGF in the pathogenesis of diabetic neuropathy , 1990, Journal of neuroscience research.

[36]  R. Coggeshall,et al.  Changes in trkA expression in the dorsal root ganglion after peripheral nerve injury , 1999, Experimental Brain Research.

[37]  R. Amann,et al.  Complete recovery by nerve growth factor of neuropeptide content and function in capsaicin-impaired sensory neurons , 1996, Brain Research.

[38]  Jocelyne Bloch,et al.  Nerve Growth Factor- and Neurotrophin-3-Releasing Guidance Channels Promote Regeneration of the Transected Rat Dorsal Root , 2001, Experimental Neurology.

[39]  R. Schicho,et al.  Increased expression of GAP-43 in small sensory neurons after stimulation by NGF indicative of neuroregeneration in capsaicin-treated rats , 1999, Regulatory Peptides.

[40]  R. Coggeshall,et al.  Preservation of sensory cells by placing stumps of transected nerve in an impermeable tube , 1989, Experimental Neurology.

[41]  R. Campenot,et al.  Receptor binding, internalization, and retrograde transport of neurotrophic factors , 2001, Cellular and Molecular Life Sciences CMLS.

[42]  J. Arezzo,et al.  Nerve growth factor administration protects against experimental diabetic sensory neuropathy , 1994, Brain Research.

[43]  R. Amann,et al.  Stimulation by nerve growth factor of neuropeptide synthesis in the adult rat in vivo: bilateral response to unilateral intraplantar injections , 1996, Neuroscience Letters.

[44]  M. Garry,et al.  Functional Regeneration of Chronically Injured Sensory Afferents into Adult Spinal Cord after Neurotrophin Gene Therapy , 2001, The Journal of Neuroscience.

[45]  C. Woolf,et al.  Regeneration of Dorsal Column Fibers into and beyond the Lesion Site following Adult Spinal Cord Injury , 1999, Neuron.

[46]  James P. Hollowell,et al.  Nerve growth factor enhances regeneration through silicone chambers , 1989, Experimental Neurology.

[47]  B. Gold.  Neuroimmunophilin ligands: evaluation of their therapeutic potential for the treatment of neurological disorders , 2000, Expert opinion on investigational drugs.

[48]  J. Glorioso,et al.  Herpes simplex-mediated gene transfer of nerve growth factor protects against peripheral neuropathy in streptozotocin-induced diabetes in the mouse. , 2002, Diabetes.

[49]  Martin E. Schwab,et al.  Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1 , 2000, Nature.

[50]  J. Kellerth,et al.  Differential effects of neurotrophins on neuronal survival and axonal regeneration after spinal cord injury in adult rats , 2002, The Journal of comparative neurology.

[51]  D. Zochodne,et al.  The microenvironment of injured and regenerating peripheral nerves , 2000, Muscle & nerve. Supplement.

[52]  L. Notterpek,et al.  Experimental models of peripheral neuropathies. , 1999, Laboratory animal science.

[53]  M. Schwab,et al.  Degeneration and regeneration of axons in the lesioned spinal cord. , 1996, Physiological reviews.

[54]  Stephen R. Rapp,et al.  Nerve Growth Factor Facilitates Regeneration across Nerve Gaps: Morphological and Behavioral Studies in Rat Sciatic Nerve , 1993, Experimental Neurology.

[55]  E. Shooter,et al.  Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: role of macrophages. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[56]  L. L. Pu,et al.  Effects of nerve growth factor on nerve regeneration through a vein graft across a gap. , 1999, Plastic and reconstructive surgery.

[57]  V. Dietz,et al.  Locomotor Recovery in Spinal Cord-Injured Rats Treated with an Antibody Neutralizing the Myelin-Associated Neurite Growth Inhibitor Nogo-A , 2001, The Journal of Neuroscience.

[58]  J. Tonra.  Classical and novel directions in neurotrophin transport and research: Anterograde transport of brain‐derived neurotrophic factor by sensory neurons , 1999, Microscopy research and technique.

[59]  S. Dib-Hajj,et al.  Changes in Expression of Two Tetrodotoxin-Resistant Sodium Channels and Their Currents in Dorsal Root Ganglion Neurons after Sciatic Nerve Injury But Not Rhizotomy , 2000, The Journal of Neuroscience.

[60]  E. Oh,et al.  Changes in nerve growth factor levels in dorsal root ganglia and spinal nerves in a rat neuropathic pain model , 1999, Experimental Brain Research.

[61]  Haining Dai,et al.  Spinal Axon Regeneration Induced by Elevation of Cyclic AMP , 2002, Neuron.

[62]  D. Zochodne,et al.  The regenerative deficit of peripheral nerves in experimental diabetes: its extent, timing and possible mechanisms. , 2000, Brain : a journal of neurology.

[63]  R. Schicho,et al.  Nerve growth factor stimulates synthesis of calcitonin gene-related peptide in dorsal root ganglion cells during sensory regeneration in capsaicin-treated rats , 1999, Neuroscience Research.

[64]  P. Distefano,et al.  Retrograde axonal transport of ciliary neurotrophic factor is increased by peripheral nerve injury , 1993, Nature.

[65]  D. Schreyer,et al.  Constitutive Expression of GAP-43 Correlates with Rapid, but Not Slow Regrowth of Injured Dorsal Root Axons in the Adult Rat , 1999, Experimental Neurology.

[66]  B. Bregman.  Regeneration in the spinal cord , 1998, Current Opinion in Neurobiology.

[67]  T. Maeda,et al.  Growth-associated protein-43 (GAP-43) in the regenerating periodontal Ruffini endings of the rat incisor following injury to the inferior alveolar nerve , 1998, Brain Research.

[68]  H. Okado,et al.  Tracing Axons in the Peripheral Nerve Using LacZ Gene Recombinant Adenovirus and Its Application to Regeneration of the Peripheral Nerve , 2001, Journal of neuropathology and experimental neurology.

[69]  Marc Rendell,et al.  Efficacy and Safety of Recombinant Human Nerve Growth Factor in Patients With Diabetic Polyneuropathy: A Randomized Controlled Trial , 2000 .

[70]  Z. Wiesenfeld‐Hallin,et al.  Differential influence of nerve growth factor on neuropeptide expression in vivo: a novel role in peptide suppression in adult sensory neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[71]  P. Distefano,et al.  Axotomy Upregulates the Anterograde Transport and Expression of Brain-Derived Neurotrophic Factor by Sensory Neurons , 1998, The Journal of Neuroscience.

[72]  B. Tedeschi,et al.  Peripheral nerve regeneration. , 1991, Neurosurgery clinics of North America.

[73]  S. Ichinose,et al.  Synthetic collagen fibers coated with a synthetic peptide containing the YIGSR sequence of laminin to promote peripheral nerve regeneration in vivo , 1999, Journal of materials science. Materials in medicine.

[74]  S. Bartlett,et al.  Molecular mechanisms regulating the retrograde axonal transport of neurotrophins , 2000, Brain Research Reviews.

[75]  C. Cheng,et al.  Neurotrophins and other growth factors in the regenerative milieu of proximal nerve stump tips , 2000, Journal of anatomy.

[76]  Deanna S. Smith,et al.  A Transcription-Dependent Switch Controls Competence of Adult Neurons for Distinct Modes of Axon Growth , 1997, The Journal of Neuroscience.

[77]  M Holmes,et al.  Sensory nerves in adult rats regenerate and restore sensory function to the skin independently of endogenous NGF , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[78]  G. Kreutzberg,et al.  Peripheral nerve regeneration: Role of growth factors and their receptors , 1993, International Journal of Developmental Neuroscience.

[79]  D. Scherman,et al.  Viral and non-viral gene therapy partially prevents experimental cisplatin-induced neuropathy , 2002, Gene Therapy.