Microglia and Trophic Factors in Neuropathic Pain States



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.


Neuropathic Pain Dorsal Horn P2X4 Receptor Peripheral Nerve Injury Spinal Dorsal Horn 
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.



allograft inflammatory factor-1


adenosine triphosphate


brain-derived neurotrophic factor


central nervous system


extracellular signal-regulated kinase


gamma amino butyric acid


ionized calcium binding adaptor protein-1


inhibitory postsynaptic current


potassium-chloride cotransporter 2


mitogen-activated protein kinase


major histocompatibility complex


N-methyl-d-aspartic acid


peripheral nerve injury




spared nerve injury


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


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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