Cell senescence in chronic pain: An integrative perspective on cellular and neural mechanisms

Chronic pain is characterized by persistent neural sensitization, yet the cellular processes underlying its maintenance remain incompletely understood. Cell senescence, has recently emerged as a potential contributor to chronic pain. In this review, we summarize evidence of senescence across multiple cell types involved in pain processing and discuss how senescent cells influence neural function through mechanisms including the senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, and epigenetic alterations. We further propose that cell senescence acts as a key link between cellular dysfunction and neural sensitization, forming a self-reinforcing network that sustains chronic pain. Importantly, targeting senescence-related pathways, including senolytics and modulators of SASP, may represent promising strategies for chronic pain therapies. This integrative perspective provides a framework for understanding chronic pain and highlights new directions for therapeutic intervention.