Phenotypic modification of primary sensory neurons: the role of nerve growth factor in the production of persistent pain

Philos Trans R Soc Lond B Biol Sci. 1996 Mar 29;351(1338):441-8. doi: 10.1098/rstb.1996.0040.

Abstract

Inflammation results in an early and maintained elevation in nerve growth factor (NGF) levels in inflamed tissues. Neutralizing the action of the increased NGF with specific anti-NGF antibodies substantially diminishes inflammatory hypersensitivity, indicating that this neurotrophin is a key mediator in the production of inflammatory pain. The hyperalgesic actions of NGF may in part be the consequence of an increase in sensitivity of the peripheral terminals of high threshold nociceptors either as a result of a direct action of NGF on trkA expressing sensory fibres or indirectly via the release of sensitizing mediators from trkA expressing inflammatory cells and postganglionic sympathetic neurons. NGF is also, however, retrogradely transported in sensory neurons to the dorsal root ganglion where it alters transcription of a number of proteins and peptides. This chapter reviews evidence suggesting that an NGF-mediated modification of gene expression in the dorsal root ganglion during inflammation is central to the pathophysiology of persistent pain. The phenotype changes produced by NGF during inflammation include elevation of neuropeptides which may amplify sensory input signals in the spinal cord and augment neurogenic inflammation in the periphery and the upregulation of growth related molecules which may lead to a hyperinnervation of injured tissue by promoting terminal sprouting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Ganglia, Spinal / physiology
  • Humans
  • Hyperalgesia / physiopathology
  • Inflammation / complications*
  • Models, Neurological
  • Nerve Growth Factors / biosynthesis
  • Nerve Growth Factors / physiology*
  • Neurons, Afferent / physiology*
  • Pain / etiology*
  • Peripheral Nerves / physiology
  • Phenotype
  • Proto-Oncogene Proteins / physiology
  • Receptor Protein-Tyrosine Kinases / physiology
  • Receptor, trkA
  • Receptors, Nerve Growth Factor / physiology
  • Substance P / biosynthesis

Substances

  • Nerve Growth Factors
  • Proto-Oncogene Proteins
  • Receptors, Nerve Growth Factor
  • Substance P
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA