Pain at the brain–heart interface: A narrative review
Pain is a frequent and clinically meaningful feature of both neurological and cardiovascular diseases, yet it is rarely examined from an integrated brain–heart perspective. Growing evidence indicates that pain perception, autonomic regulation, and cardiovascular vulnerability are closely interconnected through shared central networks, particularly the insula, cingulate cortex, and brainstem, as well as peripheral neuroimmune and neuroendocrine pathways. Despite this progress, current knowledge remains fragmented across neurology, cardiology, and pain medicine, limiting mechanistic insight and translational application. This narrative review synthesizes literature published from January 2020 to December 2025 on pain within brain–heart interactions. The synthesis highlights mechanistic pathways, clinical pain phenotypes, prognostic relevance, and emerging therapeutic strategies bridging neurological and cardiovascular domains. Key thematic areas include stroke–heart syndrome and central autonomic dysfunction, central post-stroke pain and maladaptive nociceptive processing, the role of chronic pain as a modifier of cardiovascular risk, the burden and impact of pain in heart failure and cardiac surgery survivorship, advances in neuroimaging of central autonomic networks, and the translational potential of neuromodulatory interventions such as vagal nerve and spinal cord stimulation. The reviewed evidence supports the concept of pain as a mechanistic “connector” between brain and heart diseases, influencing symptoms, disease progression, and outcomes. However, heterogeneity in pain definitions, study designs, and outcome measures continues to limit causal interpretation. A unified pain–brain–heart framework, incorporating harmonized phenotyping and mechanism-informed research, is warranted to advance precision assessment and management in this complex clinical domain.
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