title: Microglia-neuronal signalling in neuropathic pain hypersensitivity 2.0.
abstract: Microglia are increasingly recognized as critical in the pathogenesis of pain hypersensitivity caused by injury to peripheral nerves. The core signalling pathway is through P2X4 purinergic receptors on the microglia which, via the release of brain-derived neurotrophic factor, cause disinhibition of nociceptive dorsal horn neurons by raising intracellular chloride levels. This disinhibition works in synergy with enhanced excitatory synaptic transmission in the dorsal horn to transform the output of the nociceptive network. There is increased discharge output, unmasking of responses to innocuous peripheral inputs and spontaneous activity in neurons that otherwise only signal nociception. Together the changes caused by microglia-neuron signalling may account for the main symptoms of neuropathic pain in humans.
authors.affiliation: Program in Neurosciences & Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, ON M6H 2X6, Canada.
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; D002450:Cell Communication / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000502:physiology*; D008954:Models, Biological; D009437:Neuralgia / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology; D058848:Receptors, Purinergic P2X4 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002712:Chlorides; D058848:Receptors, Purinergic P2X4
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