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Major depression and chronic pain are significant health problems that seriously impact the quality of life of affected individuals. These diseases that individually are difficult to treat often co-exist, thereby compounding the patient's disability and impairment as well as the challenge of successful treatment. The development of efficacious treatments for these comorbid disorders requires a more comprehensive understanding of their linked associations through common neuromodulators, such as tumor necrosis factor-α (TNFα), and various neurotransmitters, as well as common neuroanatomical pathways and structures, including the hippocampal brain region. This review discusses the interaction between depression and chronic pain, emphasizing the fundamental role of the hippocampus in the development and maintenance of both disorders. The focus of this review addresses the hypothesis that hippocampal …