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Peripheral Nerve Injury Modulates Neurotrophin Signaling in the Peripheral and Central Nervous System

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Abstract

Peripheral nerve injury disrupts the normal functions of sensory and motor neurons by damaging the integrity of axons and Schwann cells. In contrast to the central nervous system, the peripheral nervous system possesses a considerable capacity for regrowth, but regeneration is far from complete and functional recovery rarely returns to pre-injury levels. During development, the peripheral nervous system strongly depends upon trophic stimulation for neuronal differentiation, growth and maturation. The perhaps most important group of trophic substances in this context is the neurotrophins (NGF, BDNF, NT-3 and NT-4/5), which signal in a complex spatial and timely manner via the two structurally unrelated p75NTR and tropomyosin receptor kinase (TrkA, Trk-B and Trk-C) receptors. Damage to the adult peripheral nerves induces cellular mechanisms resembling those active during development, resulting in a rapid and robust increase in the synthesis of neurotrophins in neurons and Schwann cells, guiding and supporting regeneration. Furthermore, the injury induces neurotrophin-mediated changes in the dorsal root ganglia and in the spinal cord, which affect the modulation of afferent sensory signaling and eventually may contribute to the development of neuropathic pain. The focus of this review is on the expression patterns of neurotrophins and their receptors in neurons and glial cells of the peripheral nervous system and the spinal cord. Furthermore, injury-induced changes of expression patterns and the functional consequences in relation to axonal growth and remyelination as well as to neuropathic pain development will be reviewed.

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Acknowledgments

The authors thank the Lundbeck Foundation, Simon Fougner Hartmanns Familiefond, Familien Hede-Nielsens Fond, Aase og Ejnar Danielsens Fond and PAINCAGE (European Framework Programme 7).

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  1. Danish Research Institute of Translational Neuroscience DANDRITE, Nordic EMBL Partnership, and Lundbeck Foundation Research Center MIND, Department of Biomedicine, Aarhus University, Ole Worms Allé 3, 8000, Aarhus C, Denmark

    Mette Richner, Maj Ulrichsen, Siri Lander Elmegaard, Ruthe Dieu, Lone Tjener Pallesen & Christian Bjerggaard Vaegter

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Richner, M., Ulrichsen, M., Elmegaard, S.L. et al. Peripheral Nerve Injury Modulates Neurotrophin Signaling in the Peripheral and Central Nervous System. Mol Neurobiol 50, 945–970 (2014). https://doi.org/10.1007/s12035-014-8706-9

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