Skip to main content
SpringerLink
Log in

Trophic interactions between sensory nerves and their targets

  • Review
  • Published:
Journal of Biomedical Science

Abstract

Neurotrophins are target-derived trophic factors essential for the survival and maintenance of neurons. Among these, nerve growth factor (NGF) and neurotrophin-3 (NT-3) are particularly important for sensory neurons. The actions of neurotrophins are through the p75 low-affinity receptor and the high-affinity receptor tyrosine kinase(trk). Each neurotrophin has its preferred receptor, i.e.trkA for NGF, andtrkC for NT-3. The primary sensory neurons in the dorsal root ganglion are classified into two categories, namely, the large and small sensory neurons based on their size. The large sensory neurons with the expression oftrkC depend on NT-3 for development and subserve the function of position sensations. Some of the small sensory neurons expresstrkA and are NGF-dependent. They are responsible for nociceptive sensation, the detection of painful and thermal stimuli. A more intriguing observation is the bidirectional interactions between nociceptive nerves and their target, the skin. The peripheral processes of small sensory neurons innervate the epidermis of the skin as ‘free nerve endings’. In denervated skin, there is a drastic reduction in the epidermal thickness, a finding corroborated by the phenomenon of trophic change, the shining and thinning of the skin, in the disorders of peripheral nerves. The performance of animals with peripheral nerve disorders improved after administration of neurotrophic factors. Based on these results, the therapeutic potentials of neurotrophic factors in human are under investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Airaksinen MS, Koltzenburg M, Lewin GR, Masu Y, Helbig C, Wolf E, Brem G, Toyka KV, Thoenen H, Meyer M. Specific subtypes of cutaneous mechanoreceptors require neurotrophin-3 following peripheral target innervation. Neuron 16:287–295;1996.

    Article  PubMed  Google Scholar 

  2. Anand P, Terenghi G, Warner G, Kopelman P, Williams-Chestnut RE, Sinicropi DV. The role of endogenous nerve growth factor in human diabetic neuropathy. Nature Medicine 2:703–707;1996.

    Article  PubMed  Google Scholar 

  3. Apfel SC. Neurotrophic factors in the treatment of neurotoxicity. An overview. Neurotoxicology 17:839–844;1996.

    PubMed  Google Scholar 

  4. Apfel SC, Arezzo JC, Brownlee M, Federoff H, Kessler JA. Nerve growth factor administration protects against experimental diabetic sensory neuropathy. Brain Res 634:7–12;1994.

    Article  PubMed  Google Scholar 

  5. Bhattacharyya A, Watson FL, Bradlee TA, Pomeroy SL, Stiles CD, Segal RA. Trk receptors function as rapid retrograde signal carriers in the adult nervous system. J Neurosci 17:7007–7016;1997.

    PubMed  Google Scholar 

  6. Chao MV. Neurotrophin receptors: a window into neuronal differentiation. Neuron 9:583–593;1992.

    Article  PubMed  Google Scholar 

  7. Crowley C, Spencer SD, Nishimura MC, Chen KS, Pitts-Meek S, Armanini MP, Ling LH, McMahon SB, Shelton D, Levinson AD, Phillips HS. Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons. Cell 76:1001–1012;1994.

    Article  PubMed  Google Scholar 

  8. Davies A. Neurotrophic factors and the regulation of neuronal survival in the developing peripheral nervous system. In Davies RW, Mories BJ, eds. Molecular Biology of the Neuron. Oxford, BIOS Scientific Publishers Ltd, 339–357;1997.

    Google Scholar 

  9. Davis BM, Lewin GR, Mendell LM, Jones ME, Albers KM. Altered expression of nerve growth factor in the skin of transgenic mice leads to changes in response to mechanical stimuli. Neuroscience 56:789–792;1993.

    Article  PubMed  Google Scholar 

  10. Durbec PL, Larsson-Blomberg LB, Schuchardt A, Costantini F, Pachnis V. Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts. Development 122:349–358;1996.

    PubMed  Google Scholar 

  11. Dyck PJ, Melton LJ, 3rd, O'Brien PC, Service F. Approaches to improve epidemiological studies of diabetic neuropathy. Insights from the Rochester Diabetic Neuropathy Study. Diabetes 46:Suppl 2:S5–8;1997.

    PubMed  Google Scholar 

  12. Dyck PJ, Peroutka S, Rask C, Burton E, Baker MK, Lehman KA, Gillen DA, Hokanson JL, O'Brien PC. Intradermal recombinant human nerve growth factor induces pressure allodynia and lowered heat-pain threshold in humans. Neurol 48:501–505;1997.

    Google Scholar 

  13. Ernfors P, Lee KF, Kucera J, Jaenisch R. Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Cell 77:503–512;1994.

    Article  PubMed  Google Scholar 

  14. Gao WQ, Dybdal N, Shinsky N, Murnane A, Schmelzer C, Siegel M, Keller G, Hefti F, Phillips HS, Winslow JW: Neurotrophin-3 reverses experimental cisplatin-induced peripheral sensory neuropathy. Ann Neurol 38:30–37;1995.

    Article  PubMed  Google Scholar 

  15. Hefti F. Pharmacology of neurotrophic factors. Annu Rev Pharmacol Toxicol 37:239–267;1997.

    Article  PubMed  Google Scholar 

  16. Helgren ME, Cliffer KD, Torrento K, Cavnor C, Curtis R, DiStefano PS, Wiegand SJ, Lindsay RM. Neurotrophin-3 administration attenuates deficits of pyridoxine-induced large-fiber sensory neuropathy. J Neurosci 17:372–382;1997.

    PubMed  Google Scholar 

  17. Hsieh ST, Choi S, Lin WM, Chang YC, McArthur JC, Griffin JW. Epiderminal denervation and its effects on keratinocytes and Langerhans cells. J Neurocytol 25:513–524;1996.

    PubMed  Google Scholar 

  18. Hsieh ST, Kidd GJ, Crawford TO, Xu Z, Lin WM, Trapp BD, Cleveland DW, Griffin JW. Regional modulation of neurofilament organization by myelination in normal axons. J Neurosci 14:6392–6401;1994.

    PubMed  Google Scholar 

  19. Hsieh ST, Lin WM, Chiang HY, Huang IT, Chen WP. Skin innervation and its influence on the epidermis. J Biomed Sci 4:264–268;1997.

    Article  PubMed  Google Scholar 

  20. Ip NY, Yancopoulos GD. The neurotrophins and CNTF two families of collaborative neurotrophic factors. Annu Rev Neurosci 19:491–515;1996.

    Article  PubMed  Google Scholar 

  21. Johnson EM Jr, Gorin PD, Brandeis LD, Pearson J. Dorsal root ganglion neurons are destroyed by exposure in utero to maternal antibody to nerve growth factor. Science 210:916–918;1980.

    PubMed  Google Scholar 

  22. Klein R, Silos-Santiago I, Smeyne RJ, Lira SA, Brambilla R, Bryant S, Zhang L, Snider WD, Barbacid M. Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements. Nature 368:249–251;1994.

    Article  PubMed  Google Scholar 

  23. Kopp DM, Trachtenberg JT, Thompson WJ. Glial growth factor rescues Schwann cells of mechanoreceptors from denervation-induced apoptosis. J Neurosci 17:6697–6706;1997.

    PubMed  Google Scholar 

  24. Lee KF, Li E, Huber LJ, Landis SC, Sharpe AH, Chao MV, Jaenisch R. Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Cell 69:737–749;1992.

    Article  PubMed  Google Scholar 

  25. Levi-Montalcini R, Skaper SD, Dal Toso R, Petrelli L, Leon A. Nerve growth factor: from neurotrophin to neurokine. Trends Neurosci 19:514–520;1996.

    Article  PubMed  Google Scholar 

  26. Lewin GR, Barde YA. Physiology of the neurotrophins. Annu Rev Neurosci 19:289–317;1996.

    Article  PubMed  Google Scholar 

  27. Lewin GR, Rueff A, Mendell LM. Peripheral and central mechanisms of NGF-induced hyperalgesia. Eur J Neurosci 6:1930–1912;1994.

    Google Scholar 

  28. Lewin GR, Mendell LM. Nerve growth factor and nociception. Trends Neurosci 16:353–359;1993.

    Article  PubMed  Google Scholar 

  29. Li Y, Hsieh ST, Chien H-F, Zhang X, McArthur JC, Griffin JW. Sensory and motor denervation influences epidermal thickness in rat foot glabrous skin. Exp Neurol 147:452–462;1997.

    Article  PubMed  Google Scholar 

  30. Lin WM, Hsieh ST, Huang IT, Griffin JW, Chen WP. Ultrastructural localization and regulation of protein gene product 9.5. Neuroreport 8:2999–3004;1997.

    PubMed  Google Scholar 

  31. Liu DT, Reid MT, Bridges DC, Rush RA. Denervation, but not decentralization, reduces nerve growth factor content of the mesenteric artery. J Neurochem 66:2295–2299;1996.

    PubMed  Google Scholar 

  32. Molliver DC, Wright DE, Leitner ML, Parsadanian AS, Doster K, Wen D, Yan Q, Snider WD. IB4-binding DRG neurons switch from NGF to GDNF dependence in early postnatal life. Neuron 19:849–861;1997.

    Article  PubMed  Google Scholar 

  33. Moore MW, Klein RD, Farinas I, Sauer H, Armanini M, Phillips H, Reichardt LF, Ryan AM, Carver-Moore K, Rosenthal A. Renal and neuronal abnormalities in mice lacking GDNF. Nature 382:76–79;1996.

    Article  PubMed  Google Scholar 

  34. Ordonez G, Fernandez A, Perez R, Sotelo J. Low contents of nerve growth factor in serum and submaxillary gland of diabetic mice: a possible etiological element of diabetic neuropathy. J Neurol Sci 121:163–166:1994.

    Article  PubMed  Google Scholar 

  35. Pachnis V, Mankoo B, Costantini F. Expression of the c-ret proto-oncogene during mouse embryogenesis. Development 119:1005–1017;1993.

    PubMed  Google Scholar 

  36. Parry DAD, Steinert PM. Intermediate filament structure. Curr Opin Cell Biol 4:94–98;1992.

    Article  PubMed  Google Scholar 

  37. Pichel JG, Shen L, Sheng HZ, Granholm AC, Drago J, Grinberg A, Lee EJ, Huang SP, Saarma M, Hoffer BJ, Sariola H, Westphal H. Defects in enteric innervation and kidney development in mice lacking GDNF. Nature 382:73–76;1996.

    Article  PubMed  Google Scholar 

  38. Pincelli C, Fntini F, Romualdi P, Sevignani C, Lesa G, Benassi L, Giannetti A. Substance P is diminished and vasoactive intestinal peptide is augmented in psoriatic lesions and these peptides exert disparate effects on the proliferation of cultured human keratinocytes. J Invest Dermatol 98:421–427;1992.

    Article  PubMed  Google Scholar 

  39. Ren K, Thomas DA, Dubner R. Nerve growth factor alleviates a painful peripheral neuropathy in rats. Brain Res 699:286–292;1995.

    Article  PubMed  Google Scholar 

  40. Rogers BC. Development of recombinant human nerve growth factor (rhNGF) as a treatment for peripheral neuropathic disease. Neurotoxicology 17:865–870;1996.

    PubMed  Google Scholar 

  41. Rush RA, Mayo R, Zettler C. The regulation of nerve growth factor synthesis and delivery to peripheral neurons. In: Bell C, ed. Chemical Factors in Neural Growth, Degeneration and Repair. Amsterdam, Elsevier Science B.V. 171–202;1997.

    Google Scholar 

  42. Saita K, Ohi T, Hanaoka Y, Furukawa S, Furukawa Y, Hayashi K, Matsukura S. Effects of 4-methylcatechol, a stimulator of endogenous nerve growth factor synthesis, on experimental acrylamide-induced neuropathy in rats. Neurotoxicology 16:403–412;1995.

    PubMed  Google Scholar 

  43. Sanchez MP, Silos-Santiago I, Frisen J, He B, Lira SA, Barbacid M. Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382:70–73;1996.

    Article  PubMed  Google Scholar 

  44. Schatzl HM. Neurotrophic factors: ready to go? Trends Neurosci 18:463–464;1995.

    Article  PubMed  Google Scholar 

  45. Schuchardt A, D'Agati V, Larsson-Blomberg L, Costantini F, Pachnis V. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367:380–383;1994.

    Article  PubMed  Google Scholar 

  46. Segal RA, Greenberg ME. Intracellular signaling pathways activated by neurotrophic factors. Annu Rev Neurosci 19:463–489;1996.

    PubMed  Google Scholar 

  47. Silos-Santiago I, Molliver DC, Ozaki S, Smeyne RJ, Fagan AM, Barbacid M, Snider WD. Non-trkA-expressing small DRG neurons are lost in trkA deficient mice. J Neurosci 15:5929–5942;1995.

    PubMed  Google Scholar 

  48. Smeyne RJ, Klein R, Schnapp A, Long LK, Bryant S, Lewin A, Lira SA, Barbacid M. Severe sensory and sympathetic neuropathies in mice carrying a disrupted trk/NGF receptor gene. Nature 368:246–249;1994.

    Article  PubMed  Google Scholar 

  49. Snider WD. Functions of the neurotrophins during nervous system development: what the knockouts are teaching us. Cell 77:627–638;1994.

    Article  PubMed  Google Scholar 

  50. Takahashi K, Nakanishi S, Imamura S. Direct effects of cutaneous neuropeptides on adenylyl cyclase activity and proliferation in a keratinocyte cell line: stimulation of cyclic AMP formation by CGRP and VIP/PHM, and inhibition by NPY through G protein-coupled receptors. J Invest Dermatol 101:646–651;1993.

    Article  PubMed  Google Scholar 

  51. Thomas PK, Ochoa J. Clinical features and differential diagnosis. In Dyck PJ, Thomas PK, Griffin JW, Low PA, Poduslo JF, eds. Peripheral Neuropathy. Philadelphia, W.B. Saunders, 749–774;1993.

    Google Scholar 

  52. Trupp M, Arenas E, Fainzilber M, Nilsson AS, Sieber BA, Grigoriou M, Kilkenny C, Salazar-Grueso E, Pachnis V, Arumae U, et al. Functional receptor for GDNF encoded by the c-ret proto-oncogene. Nature 381:785–788;1996.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, National Taiwan University College of Medicine, Taipei, Taiwan

    Yang-Chyuan Chang &  Sung-Tsang Hsieh

  2. Department of Anatomy, National Taiwan University College of Medicine, 1 Jen-Ai Road, Sec. 1, 10018, Taipei, Taiwan

    Wen-Pin Chen &  Sung-Tsang Hsieh

Authors
  1. Wen-Pin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yang-Chyuan Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sung-Tsang Hsieh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, WP., Chang, YC. & Hsieh, ST. Trophic interactions between sensory nerves and their targets. J Biomed Sci 6, 79–85 (1999). https://doi.org/10.1007/BF02256438

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02256438

Key Words

Search

Navigation