This review attempts to summarize and discuss contemporary pathogenetic views on vibration-induced Raynaud's phenomenon assuming its multifactorial etiology. An increase in central and peripheral sympathetic nervous activity is discussed based on different physiological indicators of autonomic dysfunction and sympathetic hyperactivity. Local acral vasodysregulation is considered. Receptor and nerve endings dysfunction presented with predominance of alpha(2)-receptor function in the digital arteries and neuronal loss in those digital cutaneous perivascular nerves containing
calcitonin gene-related peptide result in deficiency of endogenous release of this powerful
vasodilator. Endothelial damage and dysregulation induced by vibration and increased shear stresses are demonstrated by the elevated plasma level of
thrombomodulin and of
von Willebrand factor and reduced endothelium-dependent
vasodilator responses. The concentrations of
endothelin-1 are high, the highest being in most advanced stages. Decreased plasma
thiol level, indicating increased production and activity of
free radicals, contribute to vasospastic paroxysms in vibration white finger patients. Dysbalance of local vasoactive factors with opposing effects on vascular smooth muscle like
endothelin and
nitric oxide,
endothelin and
calcitonin gene-related peptide,
nitric oxide and
superoxide anion are discussed. Disturbed smooth muscle response is supposed. Changes in hemostasis, fibrinolysis and hemorrheology, activation of blood cells with erythrocyte hyperaggregation and red cell hypodeformability, platelet aggregation with increased release of vasoconstricting
thromboxane A(2) and
serotonin as well as leukocyte activation, entrapment within capillaries and post-capillary venules and increased
reactive oxygen species and lysosomal lytic
enzymes release might also contribute to digital vasospasms and tissue damage. Elevated soluble
intercellular adhesion molecule-1 levels involved in the adherence of leukocytes to endothelium and to other leukocytes have been found in patients with
hand-arm vibration syndrome.