Persistent Alterations in Microglial Enhancers in a Model of Chronic Pain

• We examined the spinal cord immune response in a model of neuropathic pain
• No infiltration of peripheral macrophages could be detected
• RNA-seq of isolated microglia revealed a transient transcriptional response
• ChIP-seq revealed persistent, injury-induced alterations of microglial enhancers

SummaryChronic 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.

Graphical AbstractFigure optionsDownload as PowerPoint slide