Research progress of depression and pain comorbidity: Animal model, mechanism, treatment strategy

Pain and depression comorbidity refers to a clinical condition in which patients experience both pain and depressive disorders. This condition is characterized by a high prevalence and complex underlying mechanisms and profoundly affects patients' quality of life. However, challenges such as therapeutic complexity and poor prognosis remain in clinical practice. This review systematically summarizes research progress in this field, including the development of animal models, potential pathogenic mechanisms, and therapeutic strategies. The animal models discussed include complete Freund's adjuvant (CFA) models, reserpine models, nerve injury models, chronic stress models, and combined models, each of which has distinct advantages and limitations. Evidence suggests that pain and depression comorbidity is associated with multiple pathological mechanisms, including hypothalamic-pituitary-adrenal (HPA) axis dysfunction, neuroinflammatory activation, and neurotransmitter imbalance. Current clinical treatment primarily adopts an integrated approach combining pharmacological interventions, psychotherapy, and physical therapy. This review aims to deepen the understanding of the mechanisms underlying pain and depression comorbidity and provide a foundation for developing novel therapeutic strategies and clinical diagnostic approaches, thereby improving patients' quality of life and reducing the disease burden.