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Microglia, Cytokines and Pain

  • E. D. Milligan
  • Ryan G. Soderquist
  • Melissa J. Mahoney
Chapter

Abstract

Chronic pain is a significant national health problem which afflicts more than 25% of adults in the United States, alone, and is the most common reason individuals seek medical care. Chronic and recurrent pain, which persists or recurs for more than 3 months, is itself a disease condition. Historically, our understanding of the creation and maintenance of neuropathic pathological pain has focused on neuronal mechanisms in the pain pathway. However, research conducted during the past ˜15 years has indicated that many of the neuronal and biochemical changes in the dorsal spinal cord are in part, initiated by and consequences of immune and glial cell signaling. Thus, conditions that activate and/or maintain activation of primary sensory neurons and dorsal spinal cord pain transmission neurons also involve surrounding glial activation. Well-characterized proinflammatory cytokines, derived from glia are critically involved in pathological pain. The most studied cytokines in pathological pain conditions are tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6. The anti-inflammatory cytokine, interleukin-10 (IL-10), is one of the most powerful counter-regulatory controls over proinflammatory function. Novel and promising viral and non-viral gene therapeutic approaches that employ the actions of anti-inflammatory cytokines such as interleukin-4 and IL-10 are being developed as novel therapeutics to treat chronic neuropathic pain conditions.

Keywords

Dorsal Root Ganglion Neuropathic Pain Dorsal Horn Complex Regional Pain Syndrome Chronic Constriction Injury 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ATP

adenosine 5′-triphosphate

BDNF

brain-derived neurotrophic factor

CCL2

a chemokine of the ‘CC’ class. Also named monocyte chemo-attractant protein; MCP-1

CCI

chronic constriction injury

CNS

central nervous system

CSF

cerebrospinal fluid

CX3CL1

a chemokine of the CX3C class. Also named fractalkine

DRG

dorsal root ganglia

GABA

gamma-aminobutyric acid

GLAST

glutamate (Glu)-aspartate (Asp) transporter; Glu-Asp transporter

GLT-1

glutamate (Glu)-transporter-1; Glu-transporter-1

HSP

heat-shock proteins

HSV

herpes simplex virus

IL-10

interleukin-10

IL-1β

interleukin 1beta

IL6

interlukin-6

IFN-γ

interferon-gamma

JAK

Janus Kinases

MyD88

myeloid differentiation 88

MAP3K

mitogen-activated protein kinase kinase kinase

MMPs

matrix metalloproteases

NF-kB

nuclear factor-kappaB

P2X

ATP-gated cation channels of the P2 purinergic receptor family

pDNA

plasmid DNA

PI3K

phosphoinositide-3 kinase

PLGA

poly(lactic-co-glycolic) acid copolymer

SOCS

suppressors of cytokine signaling

STAT

signal transducers and activators of transcription

sTNFR

TNF soluble receptor (p55)

TGF-®

transforming growth factor-beta

TIR

toll/interleukin-1 receptor

TLR

toll-like receptors

TNF-α

tumor necrosis factor-alpha

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • E. D. Milligan
    • 1
  • Ryan G. Soderquist
    • 2
  • Melissa J. Mahoney
    • 2
  1. 1.Department of NeurosciencesHealth Sciences Center, University of New MexicoAlbuquerqueUSA
  2. 2.Department of Chemical and Biological EngineeringUniversity of Colorado at BoulderBoulderUSA

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