title: Neuronal and microglial mechanisms for neuropathic pain in the spinal dorsal horn and anterior cingulate cortex.
abstract: Neuropathic pain is a debilitating chronic pain condition occurring after damage in the nervous system and is refractory to the currently available treatments. Major challenges include elucidating its mechanisms and developing new medications to treat it. Nerve injury-induced pain hypersensitivity involves aberrant excitability in spinal dorsal horn (SDH) neurons as a consequence of dysfunction of inhibitory interneurons and of hyperactivity of glial cells, especially microglia, the immune cells of the central nervous system. Evidence of this is found using animal models to investigate the molecular and cellular mechanisms of neuropathic pain. The pathologically altered somatosensory signals in the SDH then convey to the brain regions, including the anterior cingulate cortex (ACC). In these regions, nerve injury produces pre- and postsynaptic long-term plasticity, which contributes to negative emotions and anxiety associated with chronic pain conditions. Furthermore, recent evidence also indicates that the descending projection pathways from the ACC directly and indirectly to the SDH (the top-down corticospinal network) regulate nociceptive sensory transmission in the SDH. Thus, understanding a possible connection between the SDH and ACC, including a neuron-microglia interaction, may provide us with insights into the mechanisms used to amplify pain signals related to neuropathic pain and clues to aid the development of new therapeutic agents for the management of chronic pain. This article is part of the special article series "Pain".
authors.affiliation: Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Makoto
authors.identifier: 0000-0003-0585-9570
authors.initials: M
authors.lastname: Tsuda
authors.affiliation: Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.|Department of Physiology, University of Toronto, Toronto, Canada.
authors.forename: Kohei
authors.initials: K
authors.lastname: Koga
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Canada.|Department of Anatomy, Histology and Embryology, Fourth Military Medical University, Xi'an, Shaanxi, China.|Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Canada.|Center for Neuron and Disease, Frontier Institutes of Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D017628:Microglia; D009437:Neuralgia / Q000503:physiopathology*; D020671:Posterior Horn Cells; D013116:Spinal Cord / Q000503:physiopathology*; D066148:Spinal Cord Dorsal Horn
keywords: anterior cingulate cortex; microglia; neuropathic pain; spinal dorsal horn neurons; synaptic plasticity; top-down modulation