title: Molecules in pain and sex: a developing story.
abstract: Microglia are dynamic immune cells with diverse roles in maintaining homeostasis of the central nervous system. Dysregulation of microglia has been critically implicated in the genesis of neuropathic pain. Peripheral nerve injury, a common cause of neuropathic pain, engages microglia-neuronal signalling which causes disinhibition and facilitated excitation of spinal nociceptive pathways. However, recent literature indicates that the role of microglia in neuropathic pain is sexually dimorphic, and that female pain processing appears to be independent of microglia, depending rather on T cells. Despite this sex difference, pain signalling in the spinal cord converges downstream of microglia, as NMDAR-mediated facilitated excitation in pain transmitting neurons is consistent between males and females. Determining whether pain signalling is sexually dimorphic in humans and, further, addressing the sex bias in pain research will increase the translational relevance of preclinical findings and advance our understanding of chronic pain in women.
authors.affiliation: Program in Neurosciences & Mental Health, Hospital for Sick Children, Toronto, ON, Canada.|Department of Physiology, University of Toronto, Toronto, ON, Canada.|University of Toronto Centre for the Study of Pain, Toronto, ON, Canada.
authors.forename: Josiane C S
authors.initials: JC
authors.lastname: Mapplebeck
authors.affiliation: Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Beggs
authors.affiliation: Program in Neurosciences & Mental Health, Hospital for Sick Children, Toronto, ON, Canada. michael.salter@sickkids.ca.|Department of Physiology, University of Toronto, Toronto, ON, Canada. michael.salter@sickkids.ca.|University of Toronto Centre for the Study of Pain, Toronto, ON, Canada. michael.salter@sickkids.ca.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Salter
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D017628:Microglia / Q000378:metabolism; D008954:Models, Biological; D010146:Pain / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D059348:Peripheral Nerve Injuries / Q000473:pathology; D012727:Sex Characteristics; D015398:Signal Transduction
keywords: Microglia; Neuropathic Pain; Sex differences; Spinal Cord; T cells