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

R. J. Mannion, M. Costigan, I. Decosterd, F. Amaya, Q. P. Ma, J. C. Holstege, R. R. Ji, A. Acheson, R. M. Lindsay, G. A. Wilkinson, C. J. Woolf

Research output: Journal PublicationArticlepeer-review

361 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)9385-9390
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number16
DOIs
Publication statusPublished - 3 Aug 1999
Externally publishedYes

ASJC Scopus subject areas

  • General

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