The role of gut microbiota in chronic restraint stress induced comorbidity of pain and depression in female mice
Chronic stress is a major risk factor for major depressive disorder (MDD) and can induce maladaptive neurobiological alterations in pain-processing pathways, contributing to the development of hyperalgesia. Study indicated a high comorbidity rate between chronic pain and mental disorders such as anxiety and depression, with medically unexplained physical pain being particularly prominent in patients with MDD. Both preclinical and clinical studies have consistently identified neuroinflammation as a critical pathophysiological process underlying both depression and pain. Given the critical role of commensal microorganisms and their metabolites in maintaining intestinal barrier integrity, coupled with the impact of stress on gut microbial composition and homeostasis, stress-induced dysbiosis could act as a significant contributor to impaired intestinal barrier. The barrier dysfunction promotes bacterial translocation and systemic dissemination of microbial metabolites, inducing peripheral inflammation that may potentiate neuroinflammation. Collectively, gut microbial dysbiosis and impaired intestinal barrier may constitute a key underlying mechanism for chronic stress-induced pain-depression comorbidity.