Trophic Factors and Their Receptors in Pain Pathways

Chapter

Abstract

Trophic factors play a key role in the plasticity of pain pathways. They shape the circuitry and neurochemistry of acute pain pathways and also contribute to changes that occur in chronic inflammatory and neuropathic pain. Adult dorsal root ganglion (DRG) neurons express neurotrophin receptors and localization studies have shown that different DRG subtypes express different receptors. Thus large diameter neurons (low threshold mechanoreceptors) express either trkB (the receptor for BDNF) or trkC (the receptor for neurotrophin-3, NT-3) and small diameter neurons express trkA (the receptor for nerve growth factor, NGF). However the trkA expression is confined to the population of nociceptors that constitutively express neuropeptides (peptidergic nociceptors). Another population of nociceptors exists (non-peptidergic nociceptors) which normally do not express neuropeptides, which can be identified using the lectin Griffonia simplifolia IB4, and which express receptor components for GDNF. After nerve injury or inflammation major changes take place that contribute to the development of chronic pain and many of these changes appear to be driven by changes in the availability of growth factors. The role of NGF in such changes has been well documented but less is known about the role of GDNF. However there is growing evidence that endogenous GDNF contributes to inflammatory pain, and that exogenous GDNF can be used to treat neuropathic pain. In each case the GDNF effects are mediated primarily by the non-peptidergic (IB4) population of nociceptors. There is also evidence that neuropoetic cytokines act on non-peptidergic nociceptors.

Keywords

Formaldehyde Tyrosine Aldehyde Polypeptide NMDA 

Abbreviations

BDNF

brain derived neurotrophic factor

CCI

chronic constriction injury

CGRP

calcitonin gene-related peptide

CFA

complete Freund’s adjuvant

CNTF

ciliary neurotrophic factor

DRG

dorsal root ganglion

GDNF

glial cell-derived neurotrophic factor

IB4

isolectin B4

IL6

inteleukin 6

LIF

leukaemia inhibitory factor

MCP-1

monocyte chemoattractant protein 1

NGF

nerve growth factor

OM

oncostatin M

NPY

neuropeptide Y

SNL

spinal nerve ligation

Trk

tropomyosin kinase

TRP

transient receptor potential (ion channels)

VIP

vasoactive intestinal peptide

Notes

Acknowledgments

Many thanks to Dr Marzia Malcangio and Dr Bared Safieh-Garabedian for helpful suggestions and comments on the draft manuscript.

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Barts and The London School of Medicine and DentistryInstitute of Cell and Molecular Science, Neuroscience Centre, Queen Mary University of LondonWhitechapelUK

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