Microglia, Cytokines and Pain

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


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.


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.



adenosine 5′-triphosphate


brain-derived neurotrophic factor


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


chronic constriction injury


central nervous system


cerebrospinal fluid


a chemokine of the CX3C class. Also named fractalkine


dorsal root ganglia


gamma-aminobutyric acid


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


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


heat-shock proteins


herpes simplex virus




interleukin 1beta






Janus Kinases


myeloid differentiation 88


mitogen-activated protein kinase kinase kinase


matrix metalloproteases


nuclear factor-kappaB


ATP-gated cation channels of the P2 purinergic receptor family


plasmid DNA


phosphoinositide-3 kinase


poly(lactic-co-glycolic) acid copolymer


suppressors of cytokine signaling


signal transducers and activators of transcription


TNF soluble receptor (p55)


transforming growth factor-beta


toll/interleukin-1 receptor


toll-like receptors


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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