Skip to main content

Advertisement

Log in

Influence of human skin injury on regeneration of sensory neurons

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The regeneration of sensory nerve fibres is regulated by trophic factors released from their target tissue, particularly the basal epidermis, and matrix molecules. Means to modulate this response may be useful for the treatment of neuromas and painful hypertrophic scars and of sensory deficits in skin grafts and flaps. We have developed an in vitro model of sensory neuron regeneration on human skin in order to study the mechanisms of sensory dysfunction in pathological conditions. Adult rat sensory neurons were co-cultured with unfixed cryosections of normal or injured (crushed) human skin for 72 h. Neurons were immunostained for growth-associated protein-43 and the neurite lengths of neuronal cell bodies situated in various skin regions were measured. Two-way analysis of variance was performed. Neurites of sensory cell bodies on epidermis of normal skin were the shortest, with a mean ± SEM of 75±10 μm, whereas those of cells on the dermo-epidermal junction were the longest, with a mean ± SEM of 231±18 μm. Neurons on the dermo-epidermal junction of injured skin had significantly longer neurites than those on the same region of normal skin (mean ± SEM = 289±21 μm). Regeneration of sensory neurons may be influenced by extracellular matrix molecules, matrix-binding growth factors and trophic factors. Altered substrate or trophic factors in injured skin may explain the increase of neurite lengths. This in vitro model may be useful for studying the molecular mechanisms of sensory recovery and the development of neuropathic pain following peripheral nerve injury.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3A, B.
Fig. 4.

Similar content being viewed by others

References

  • Anand P (1995) Nerve growth factor regulates nociception in human health and disease. Br J Anaesth 75:201–208

    CAS  PubMed  Google Scholar 

  • Anand P (1996) Neurotrophins and peripheral neuropathy. Philos Trans R Soc Lond Biol 351:449–454

    CAS  PubMed  Google Scholar 

  • Anand U, McMahon SB, Cohen J (1996) Preferential growth of neonatal rat dorsal root ganglion cells on homotypic peripheral nerve substrates in vitro. Eur J Neurosci 8:649–657

    CAS  PubMed  Google Scholar 

  • Bottenstein JE, Sato GH (1979) Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc Natl Acad Sci USA 76:514–517

    CAS  PubMed  Google Scholar 

  • Carbonetto S, Evans D, Cochard P (1987) Nerve fiber growth in culture on tissue substrata from central and peripheral nervous systems. J Neurosci 7:610–620

    CAS  PubMed  Google Scholar 

  • Curtis R, Green D, Lindsay RM, Wilkin GP (1993) Up-regulation of GAP-43 and growth of axons in rat spinal cord after compression injury. J Neurocytol 22:51–64

    CAS  PubMed  Google Scholar 

  • Davies AM, Bandtlow C, Heumann R, et al (1987) Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. Nature 326:353–358

    CAS  PubMed  Google Scholar 

  • Fantini F, Magnoni C, Bracci-Laudiero L, Pincelli CT (1995) Nerve growth factor is increased in psoriatic skin. J Invest Dermatol 105:854–855

    CAS  PubMed  Google Scholar 

  • Hökfelt T (1991) Neuropeptides in perspective: the last ten years. Neuron 7:867–879

    PubMed  Google Scholar 

  • Jones NF (1996) Treatment of chronic pain by "wrapping" intact nerves with pedicle and free flaps. Hand Clin 12:765–772

    CAS  PubMed  Google Scholar 

  • Kennedy AJ, Wellmer A, Facer P, et al (1998) Neurotrophin-3 is increased in skin in human diabetic neuropathy. J Neurol Neurosurg Psychiatry 65:393–395

    CAS  PubMed  Google Scholar 

  • Kruger L, Perl ER, Sedivec MJ (1981) Fine structure of myelinated mechanical nociceptor endings in cat hairy skin. J Comp Neurol 198:137–154

    CAS  PubMed  Google Scholar 

  • Lahteenmaki T, Waris T, Asko-Seljavaara S, Sundell B (1989) Recovery of sensation in free flaps. Scand J Plast Reconstr Surg Hand Surg 23:217–222

    CAS  PubMed  Google Scholar 

  • Lisney SJ (1989) Regeneration of unmyelinated axons after injury of mammalian peripheral nerve. Q J Exp Physiol 74:757–784

    CAS  PubMed  Google Scholar 

  • Lundborg G (2000) A 25-year perspective of peripheral nerve surgery: evolving neuroscientific concepts and clinical significance. J Hand Surg [Am] 25:391–414

    Google Scholar 

  • Parkhouse N, Crowe R, McGrouther DA, Burnstock G (1992) Painful hypertrophic scarring and neuropeptides. Lancet 340:1410

    CAS  Google Scholar 

  • Pincelli C, Yaar M (1997) Nerve growth factor: its significance in cutaneous biology. J Invest Dermatol Symp Proc 2:31–36

    CAS  Google Scholar 

  • Raja SN, Meyer RA, Ringkamp M, Campbell JN (1999) Peripheral neural mechanisms of nociception. In: Wall PD, Melzack R (eds) Textbook of pain. Churchill Livingstone, Edinburgh, pp 11–57

  • Rath S, Green CJ (1991) Lack of topographical specificity in sensory nerve regeneration through muscle grafts in rats. J Hand Surg [Br] 16:524–530

    Google Scholar 

  • Sloan EP (1993) Nerve injuries in the hand. Emerg Med Clin North Am 11:651–670

    CAS  PubMed  Google Scholar 

  • Sood MK, Elliot D (1998) Treatment of painful neuromas of the hand and wrist by relocation into the pronator quadratus muscle. J Hand Surg [Br] 23:214–9

    Google Scholar 

  • Sunderland SS (1991) Nerve injuries and their repair. A critical appraisal. Churchill Livingstone, Edinburgh

  • Tonge DA, Golding JP, Edbladh M, Kroon M, Ekstrom PE, Edstrom A (1997) Effects of extracellular matrix components on axonal outgrowth from peripheral nerves of adult animals in vitro. Exp Neurol 146:81–90

    Article  CAS  PubMed  Google Scholar 

  • Uitto J, Mauviel A, McGrath J (1996) The dermal-epidermal basement membrane zone in cutaneous wound healing. In: Clark RF (ed) The molecular and cellular biology of wound repair. Plenum, New York, pp 513–553

  • Werner A, Willem M, Jones LL, Kreutzberg GW, Mayer U, Raivich G (2000) Impaired axonal regeneration in alpha 7 integrin-deficient mice. J Neurosci 20:1822–1830

    Google Scholar 

  • Wehrle-Haller B, Chiquet M (1993) Dual function of tenascin: simultaneous promotion of neurite growth and inhibition of glial migration. J Cell Sci 106:597–610

    CAS  PubMed  Google Scholar 

  • Woolf CJ (1996) Phenotypic modification of primary sensory neurons: the role of nerve growth factor in the production of persistent pain. Philos Trans R Soc Lond Biol 351:441–448

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Professor Nick Wright for support and facilities at Cancer Research UK, London.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P. Anand.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taherzadeh, O., Otto, W.R., Anand, U. et al. Influence of human skin injury on regeneration of sensory neurons. Cell Tissue Res 312, 275–280 (2003). https://doi.org/10.1007/s00441-003-0724-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-003-0724-2

Keywords

Navigation