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

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.

• Authors: 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
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 96 Issue 16 Pg. 9385-90 (Aug 03 1999) ISSN: 0027-8424 [Print] United States
• PMID: 10430952 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• Animals
• Axonal Transport
• Brain-Derived Neurotrophic Factor (genetics)
• Decerebrate State
• Electric Stimulation
• Ganglia, Spinal (physiology, 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, physiology)
• Receptor, Ciliary Neurotrophic Factor
• Receptors, Nerve Growth Factor (genetics, physiology)
• Recombinant Fusion Proteins (pharmacology)
• Spinal Cord (physiology, physiopathology)
• Time Factors
• Touch
• Transcription, Genetic