Recent progress in chronic pain-related negative emotions and cognitive dysfunction: insights into the mechanisms underlying neural circuitry

Pain is a complex sensory and affective experience that is frequently accompanied by comorbid conditions such as anxiety, depression, fear, and cognitive dysfunction, collectively exacerbating patient suffering and disease burden. Despite significant advancements in pain research, the mechanisms underlying chronic pain and its related negative emotions remain inadequately understood. The cerebral cortex, lateral habenula (LHb), thalamus, amygdala, parabrachial nucleus (PBN), hippocampus, and locus coeruleus (LC) are widely associated with chronic pain, chronic pain-related negative emotions, and cognitive dysfunction. In this review, we summarize recent research on the functions of various brain nuclei and their subregions in chronic pain and related negative emotions and cognitive dysfunction from the perspective of neural circuits. By delineating these circuit-level mechanisms, we aim to provide insights that may inform the development of more effective strategies for the clinical diagnosis and treatment of chronic pain and comorbid emotional and cognitive dysfunctions.