Neurotrophins: peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity

Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9385-90. doi: 10.1073/pnas.96.16.9385.


Brain-derived neurotrophic factor (BDNF) is expressed in nociceptive sensory neurons and transported anterogradely to the dorsal horn of the spinal cord where it is located in dense core vesicles in C-fiber terminals. Peripheral inflammation substantially up-regulates BDNF mRNA and protein in the dorsal root ganglion (DRG) in a nerve growth factor-dependent fashion and results in novel expression of BDNF by DRG neurons with myelinated axons. C-fiber electrical activity also increases BDNF expression in the DRG, and both inflammation and activity increase full-length TrkB receptor levels in the dorsal horn. Sequestration of endogenous BDNF/neurotrophin 4 by intraspinal TrkB-Fc fusion protein administration does not, in noninflamed animals, change basal pain sensitivity nor the mechanical hypersensitivity induced by peripheral capsaicin administration, a measure of C fiber-mediated central sensitization. TrkB-Fc administration also does not modify basal inflammatory pain hypersensitivity, but does block the progressive hypersensitivity elicited by low-intensity tactile stimulation of inflamed tissue. BDNF, by virtue of its nerve growth factor regulation in sensory neurons including novel expression in A fibers, has a role as a central modulator of tactile stimulus-induced inflammatory pain hypersensitivity.

Publication types

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

MeSH terms

  • Animals
  • Axonal Transport
  • Brain-Derived Neurotrophic Factor / genetics*
  • Decerebrate State
  • Electric Stimulation
  • Ganglia, Spinal / physiology
  • Ganglia, Spinal / physiopathology
  • Gene Expression Regulation*
  • In Situ Hybridization
  • Inflammation / physiopathology*
  • Male
  • Motor Neurons / physiology
  • Nerve Fibers / physiology
  • Neurons, Afferent / physiology*
  • Pain / physiopathology*
  • Physical Stimulation
  • Protein Biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / physiology
  • Recombinant Fusion Proteins / pharmacology
  • Spinal Cord / physiology*
  • Spinal Cord / physiopathology
  • Time Factors
  • Touch
  • Transcription, Genetic


  • Brain-Derived Neurotrophic Factor
  • RNA, Messenger
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Nerve Growth Factor
  • Recombinant Fusion Proteins
  • Receptor Protein-Tyrosine Kinases