title: The known knowns of microglia-neuronal signalling in neuropathic pain.
abstract: Microglia are key cellular mediators of plasticity in the spinal cord that drives the development and maintenance of pain hypersensitivity following peripheral nerve damage. An essential reactive microglial phenotype is characterized by induced expression of purinergic P2X4 receptors. Activation of these receptors initiates a core microglial-neuronal signalling pathway which through disinhibition transforms the output of dorsal horn neurons projecting to the brain pain networks. Here we describe recent advances in elucidating molecules that regulate key aspects of this core pathway, and opportunities for targeting critical signalling hubs to treat neuropathic pain.
authors.affiliation: Program in Neurosciences & Mental Health, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. Electronic address: simon.beggs@gmail.com.
authors.forename: Simon
authors.initials: S
authors.lastname: Beggs
authors.forename: Michael W
authors.initials: MW
authors.lastname: Salter
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D006801:Humans; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000378:metabolism; D058848:Receptors, Purinergic P2X4 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D058848:Receptors, Purinergic P2X4
keywords: BDNF; Microglia; P2X4; Spinal cord