Chronic pain, memory, and adult hippocampal neurogenesis: Current advances, insights, and future directions

Beyond the sensory dimension, chronic pain commonly disrupts cognitive function, with memory loss being a frequent and debilitating complaint that complicates treatment. Memory impairment has been observed in multiple animal models of chronic pain. This review summarizes the literature related to memory impairment induced by chronic pain across species. Increasing evidence suggests that chronic pain affects adult hippocampal neurogenesis by disrupting the proliferation and survival of newborn granular cells. Given that adult hippocampal neurogenesis is critical for learning and memory processing, we focused on recent preclinical studies on the role of adult hippocampal neurogenesis in memory impairment induced by chronic pain. Based on the collected evidence, we postulated that chronic pain reduces adult hippocampal neurogenesis, thereby contributing to memory impairments. We also considered the intrinsic and circuit mechanisms in the hippocampus by which chronic pain leads to adult hippocampal neurogenesis injury and memory impairment. In this review, we emphasize the role of brain-derived neurotrophic factor supplementation in the dentate gyrus and local inflammatory factors, including cytokine release and glial activation. Future research aimed at deciphering the precise mechanisms underlying impairments in adult hippocampal neurogenesis in chronic pain may help identify novel biomarkers for early diagnosis and inspire the development of non-invasive neuromodulation or pro-neurogenic therapies tailored for chronic pain patients with cognitive comorbidities.