Astrogliopathology: A core pathogenic factor in diabetic neuropathic pain

Diabetic neuropathic pain (DNP) is one of the most common chronic complications in diabetic patients, severely impacting the quality of life, physical and mental health, while imposing economic burdens on patients. Due to the limited understanding of the complex pathogenesis of DNP, current prevention and treatment approaches remain inadequate. Astrocytes, as the most abundant glial cells in the central nervous system (CNS), play a critical role in pain regulation. Recent studies have demonstrated that various pathological changes in astrocytes contribute to the development and progression of DNP; importantly, reversing these astrogliopathological changes can alleviate pain and mitigate diabetes-associated neuropathy. This review systematically summarizes the primary physiological functions and key cellular structures of astrocytes in the CNS, and categorizes their pathological phenotypes, including reactive astrogliosis, astrodegeneration with astroglial atrophy and loss of function, and astroglial pathological remodelling. Furthermore, we elaborated on common astrogliopathological phenotypes observed in DNP, explored their specific roles in DNP pathogenesis, evaluated the efficacy of existing astrocyte-targeted therapeutic strategies, and highlighted outstanding questions and future research directions. This study aims to synthesize recent advances in astrogliopathological changes and DNP, providing novel insights for improving disease management and pain relief in DNP.