Microglia and Trophic Factors in Neuropathic Pain States

Chapter

Abstract

Neuropathic pain is a complex phenomenon and abundant evidence suggests it involves molecular and cellular physiological, structural and pharmacological changes within the peripheral and central nervous systems. Traditionally considered to be mediated by neuronal changes, it is now becoming increasingly clear that neuro-immune interactions are key mediators of neuropathic pain states. Following peripheral nerve injury in adults, through an as yet not fully understood process, the peripherally injured neurons signal to spinal microglia and induce their activation and proliferation. A key change is the upregulation of microglial P2X4 receptors; ATP acting on P2X4 receptors cause microglia to synthesize and release BNDF which in turn signal through neuronal TrkB receptors to cause a downregulation of KCC2. This results in a disruption of the cellular chloride homeostasis, impairing inhibition and increasing neuronal excitability. Microglia can no longer be regarded as simply immune effectors of the CNS, clearing cellular debris. It is now evident that they are crucial mediators of neuro-immune signaling, controlling neuronal excitability and contributing to the pathology of post-injury pain states.

Keywords

Migration NMDA 

Abbreviations

AIF-1

allograft inflammatory factor-1

ATP

adenosine triphosphate

BDNF

brain-derived neurotrophic factor

CNS

central nervous system

ERK

extracellular signal-regulated kinase

GABA

gamma amino butyric acid

Iba1

ionized calcium binding adaptor protein-1

IPSC

inhibitory postsynaptic current

KCC2

potassium-chloride cotransporter 2

MAPK

mitogen-activated protein kinase

MHC

major histocompatibility complex

NMDA

N-methyl-d-aspartic acid

PNI

peripheral nerve injury

PPADS

pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate

SNI

spared nerve injury

TNP-ATP

2′′,3′′-O-(2,4,6-trinitrophenyl)adenosine 5′′-triphosphate

TrkB

tropomyosin-related kinase B

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Program in Neurosciences & Mental Health, Centre for the Study of Pain, Hospital for Sick ChildrenUniversity of TorontoTorontoCanada, M5G 1X8

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