title: Persistent Alterations in Microglial Enhancers in a Model of Chronic Pain.
abstract: Chronic pain is a common and devastating condition that induces well-characterized changes in neurons and microglia. One major unanswered question is why these changes should persist long after the precipitating injury has healed. Here, we suggest that some of the longer-lasting consequences of nerve injury may be hidden in the epigenome. Cell sorting and sequencing techniques were used to characterize the spinal cord immune response in a mouse model of chronic neuropathic pain. Infiltration of peripheral myeloid cells was found to be absent, and RNA sequencing (RNA-seq) of central microglia revealed transient gene expression changes in response to nerve ligation. Conversely, examination of microglial enhancers revealed persistent, post-injury alterations in close proximity to transcriptionally regulated genes. Enhancers are regions of open chromatin that define a cell's transcription factor binding profile. We hypothesize that changes at enhancers may constitute a mechanism by which painful experiences are recorded at a molecular level.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, UK. Electronic address: franziska.denk@kcl.ac.uk.
authors.forename: Franziska
authors.initials: F
authors.lastname: Denk
authors.affiliation: Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Woodbury, NY 11797, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Crow
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, UK.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Didangelos
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, UK.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Lopes
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, UK. Electronic address: stephen.mcmahon@kcl.ac.uk.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McMahon
mesh_terms: D000818:Animals; D059350:Chronic Pain / Q000235:genetics* / Q000473:pathology*; D004195:Disease Models, Animal; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D016678:Genome; D008026:Ligation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism* / Q000473:pathology*; D015203:Reproducibility of Results; D013116:Spinal Cord / Q000473:pathology; D013127:Spinal Nerves / Q000473:pathology; D014158:Transcription, Genetic