Vascular Pain: A Narrative Review on Venous Leg Ulcers

Vascular pain encompasses a heterogeneous group of clinical conditions characterized by pain arising from arterial, venous, microvascular, or vasculitic mechanisms. Unlike classical nociceptive pain, vascular pain often displays mixed nociceptive, neuropathic, and nociplastic components, reflecting ischemia, endothelial dysfunction, neuroinflammation, and maladaptive central sensitization. Clinically, vascular pain is encountered in chronic limb-threatening ischemia (CLTI), venous leg ulcers (VLU), sickle cell disease (SCD), and systemic vasculitides, imposing a major burden on quality of life, functionality, and health systems. Its recognition remains challenging due to overlapping mechanisms and atypical pain presentations. Advances in pathophysiological understanding and the development of targeted interventions—ranging from revascularization and spinal cord stimulation to novel pharmacological and bioengineering approaches—are reshaping management. This narrative review synthesizes current evidence on mechanisms, clinical manifestations, diagnostic approaches, and therapeutic strategies for vascular pain, highlighting gaps in knowledge and directions for future research.