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Microglia, Cytokines and Pain

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Synaptic Plasticity in Pain

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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.

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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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Authors and Affiliations

  1. Department of Neurosciences, Health Sciences Center, University of New Mexico, Albuquerque, NM 87131-0001, USA

    E. D. Milligan

  2. Department of Chemical and Biological Engineering, University of Colorado at Boulder, Boulder, CO, USA

    Ryan G. Soderquist & Melissa J. Mahoney

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  1. E. D. Milligan
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  2. Ryan G. Soderquist
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  3. Melissa J. Mahoney
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Correspondence to E. D. Milligan .

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    Milligan, E.D., Soderquist, R.G., Mahoney, M.J. (2009). Microglia, Cytokines and Pain. In: Malcangio, M. (eds) Synaptic Plasticity in Pain. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0226-9_17

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