A vascular mechanistic approach to understanding Raynaud phenomenon

During exposure to cold, our bodies attempt to maintain normal core temperature by restricting heat loss through cutaneous vasoconstriction, and by increasing heat production through shivering and nonshivering thermogenesis. In selected areas of human skin (including on the fingers and toes), the vascular system has specialized structural and functional features that enable it to contribute to thermoregulation. These features include arteriovenous anastomoses, which directly connect the arterial and venous systems and bypass the nutritional capillaries supplying blood to the skin tissue. Of note, Raynaud phenomenon predominantly affects the arterial territories supplying these specialized areas of skin. Indeed, Raynaud phenomenon can be considered a disorder of vascular thermoregulatory control. This Review presents an understanding of Raynaud phenomenon in the context of vascular and thermoregulatory control mechanisms, including the role of unique thermosensitive vascular structural and functional specialization, and describes the potential role of thermogenesis in this disorder. This new approach provides remarkable insight into the disease process and builds a framework to critically appraise the existing knowledge base. This paradigm also explains the deficiencies in some current therapeutic approaches, and highlights new areas of potential relevance to the pathogenesis and treatment of Raynaud phenomenon that should be expanded and explored.