Persistent Alterations in Microglial Enhancers in a Model of Chronic Pain

Franziska Denk, Megan Crow, Athanasios Didangelos, Douglas M. Lopes, Stephen B. McMahon

Research output: Contribution to journalArticlepeer-review

107 Citations (Scopus)
212 Downloads (Pure)

Abstract

Summary:
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.
Original languageEnglish
Pages (from-to)1771–1781
JournalCell Reports
Volume15
Issue number8
Early online date12 May 2016
DOIs
Publication statusPublished - 24 May 2016

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