Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence.

ABSTRACT: Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Ana

SUBMITTER: Muralidharan A 

PROVIDER: S-EPMC9012275 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature