The transition from acute to chronic pain: dynamic epigenetic reprogramming of the mouse prefrontal cortex up to 1 year after nerve injury.
Pain
; 161(10): 2394-2409, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32427748
ABSTRACT
Chronic pain is associated with persistent structural and functional changes throughout the neuroaxis, including in the prefrontal cortex (PFC). The PFC is important in the integration of sensory, cognitive, and emotional information and in conditioned pain modulation. We previously reported widespread epigenetic reprogramming in the PFC many months after nerve injury in rodents. Epigenetic modifications, including DNA methylation, can drive changes in gene expression without modifying DNA sequences. To date, little is known about epigenetic dysregulation at the onset of acute pain or how it progresses as pain transitions from acute to chronic. We hypothesize that acute pain after injury results in rapid and persistent epigenetic remodelling in the PFC that evolves as pain becomes chronic. We further propose that understanding epigenetic remodelling will provide insights into the mechanisms driving pain-related changes in the brain. Epigenome-wide analysis was performed in the mouse PFC 1 day, 2 weeks, 6 months, and 1 year after peripheral injury using the spared nerve injury in mice. Spared nerve injury resulted in rapid and persistent changes in DNA methylation, with robust differential methylation observed between spared nerve injury and sham-operated control mice at all time points. Hundreds of differentially methylated genes were identified, including many with known function in pain. Pathway analysis revealed enrichment in genes related to stimulus response at early time points, immune function at later time points, and actin and cytoskeletal regulation throughout the time course. These results emphasize the importance of considering pain chronicity in both pain research and in treatment optimization.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dor Crônica
/
Traumatismos dos Nervos Periféricos
Limite:
Animals
Idioma:
En
Revista:
Pain
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Canadá