Mechanisms of comorbidity between Alzheimer's disease and pain

Clinical studies have revealed a significant correlation between pain and neurodegenerative diseases, particularly Alzheimer's disease (AD). However, due to cognitive and speech impairments, AD patients, especially those in moderate to severe stages, are often overlooked in pain management. The challenges in obtaining pain-related information from this population exacerbate the issue. Although recent clinical research has increasingly recognized the comorbidity of AD and pain, the pathological alterations and interactive mechanisms underlying this relationship remain inadequately explored. This review provides a comprehensive analysis of the clinical features and pathological mechanisms of AD with and without pain comorbidity. It examines underlying processes, including neuroinflammation, peripheral-central immune interactions, and neurotransmitter dynamics. Furthermore, it highlights current pain assessment and management strategies in AD patients. By offering a theoretical framework, this review aims to support the development of effective pain management approaches and serve as a reference for clinical interventions targeting AD-associated pain. HIGHLIGHTS: The comorbidity between AD and CP encompasses multiple interrelated biological pathways, such as neurodegeneration and inflammatory responses. The damage to neurons and synapses in AD patients influences the brain regions responsible for processing pain, thereby reducing the pain response. Neuroinflammation plays a vital role in the development of both AD and CP. Enhanced inflammatory responses have an impact on the CNS and promote sensitization. Common neurotransmitter alterations exist in the comorbidity of AD and CP, influencing cognition, emotion, and pain perception.