Pain represents a critical yet underexplored interface between brain and heart diseases, reflecting complex bidirectional interactions among neural, cardiovascular, immune, and psychosocial systems. This special issue of Brain and Heart is dedicated to advancing a mechanistic and translational understanding of pain as both a symptom and a disease modifier in neurological and cardiovascular disorders.

Central nervous system injuries, such as stroke and neurodegenerative conditions, frequently alter pain perception through maladaptive neuroplasticity, central sensitization, and dysregulation of descending inhibitory pathways. Conversely, cardiac diseases, including ischemic heart disease, heart failure, and arrhythmias, are often accompanied by acute and chronic pain syndromes that are modulated by autonomic imbalance, neuroinflammation, and altered brain-heart signaling. Importantly, pain itself can exacerbate cardiovascular risk via sustained sympathetic activation, hypothalamic-pituitary-adrenal axis engagement, and behavioral consequences such as reduced physical activity, sleep disturbance, and mood disorders.

This issue would bring together interdisciplinary contributions spanning basic neuroscience, cardiology, pain medicine, imaging, and digital health. Topics include neurocardiology of pain, shared inflammatory and neuroimmune mechanisms, central processing of cardiac pain, post-stroke and post-cardiac surgery pain syndromes, and emerging roles of biomarkers, neuromodulation, and artificial intelligence in risk stratification and personalized management. By integrating brain- and heart-centered perspectives, this collection aims to promote a unified, mechanism-based framework for pain assessment and treatment, ultimately improving outcomes in patients with complex brain-heart disease interactions.