Does maladaptive microvascular flow redistribution cause tissue hypoxia in fibromyalgia?

Fibromyalgia is a chronic pain syndrome characterized by widespread pain, fatigue, and cognitive complaints often described by patients as "brain fog". In the absence of specific physiological, laboratory, or imaging markers, diagnosis remains clinical. Despite extensive investigation, its underlying mechanisms remain unclear. While altered pain processing (known also as "central sensitization") has long dominated explanatory models, accumulating evidence suggests contributory peripheral physiological abnormalities. Reported findings include normal arterial oxygenation alongside reduced tissue oxygen saturation, relatively elevated venous oxygen saturation, and increased tissue lactate, collectively indicating impaired tissue oxygen extraction. Studies examining microcirculatory abnormalities as a causal mechanism have yielded inconsistent results. We propose that fibromyalgia may involve maladaptive capillary-level blood flow distribution prioritizing metarteriolar thoroughfare channels, physiological low-resistance microvascular pathways involved in vasomotion and flow regulation. If this regulatory mechanism becomes maladaptive, blood flow may preferentially bypass exchange capillaries, reducing local oxygen availability below metabolic demand and producing intermittent tissue hypoxia. This hypoxic stress may contribute directly to pain, tenderness, and fatigue and may arise locally or through impaired autonomic regulation of vasomotion. This model offers a potential explanation for the paradox of tissue hypoxia despite preserved systemic oxygen delivery and generates testable physiological predictions. However, current evidence remains circumstantial, and the proposed mechanism requires empirical validation.