The Role of Neuroimmune Interactions and Glial Cell Regulation in Pain-Depression Comorbidity

Pain and depression frequently co-occur in clinical settings, mutually exacerbating each other and forming a vicious cycle that significantly impairs patients’ quality of life. However, the underlying mechanisms of this comorbidity remain incompletely understood. Traditional theories have primarily focused on aberrant neural circuits and monoaminergic neurotransmitter imbalances. Recent studies, however, suggest that the neuroimmune system—particularly glial cells within the central nervous system—plays a critical role in the onset and progression of pain–depression comorbidity. This review systematically summarizes advances in research on neuroimmune responses in pain–depression comorbidity, with a particular emphasis on glial cell–mediated dysregulation of central immune homeostasis. Our aim is to provide new insights into the pathophysiological mechanisms underlying this comorbidity and to lay a theoretical foundation for the development of novel therapeutic strategies.