Mechanisms of Raynaud’s disease

Abstract

Raynaud's phenomenon is due to transient cessation of blood flow to the digits of the hands or feet. An attack of Raynaud’s phenomenon is classically manifested as triphasic color changes. The white phase is due to excessive vasoconstriction and cessation of regional blood flow. This phase is followed by a cyanotic phase, as the residual blood in the finger desaturates. The red phase is due to hyperemia as the attack subsides and blood flow is restored. An attack is frequently associated with pain and/or paresthesia due to sensory nerve ischemia. Variants of Raynaud’s phenomenon include acrocyanosis and primary livedo reticularis, each of which is associated with reduced skin blood flow, exacerbated by cold or emotional upset. Raynaud’s phenomenon in the absence of other disorders is primary Raynaud’s phenomenon, or Raynaud’s disease. The mechanisms of Raynaud’s disease include increased activation of the sympathetic nerves, in response to cold or emotion; an impaired habituation of the cardiovascular response to stress may contribute. In addition, there appears to be a local fault, which is likely multifactorial. This local fault is due to an alteration in vascular function rather than vascular structure. The alteration in vascular function may be related to increased sensitivity to cold of the adrenergic receptors on the digital artery vascular smooth muscle. In some cases, locally released or systemically circulating vasoconstrictors may participate, including endothelin, 5-hydroxytryptamine and thromboxane. A deficiency or increased degradation of nitric oxide, possibly due to increased oxidative stress, may be involved in some cases. These recent pathophysiological insights may lead to new therapeutic options.

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

“…Cold acra have been found in FS similar to Raynaud's phenomenon (CREST) or even Raynaud's disease, yet less pronounced [98]. The role of endothelial dysfunction in primary and secondary Raynaud's phenomenon has been demonstrated with evidence from various modalities including autonomic nervous stress tests like the cold pressor test [121][122][123][124][125]. It may be regarded a heterogeneous syndrome involving endothelial dysfunction as a key player but not every form entails a propensity for atherosclerosis.…”

Feeling of Cold Hands and Feet is a Highly Heritable Phenotype

“…A diagnosis of Raynaud's phenomenon (RP) can be made when color changes occur to the skin of the digits of the hands or feet in response to cold temperatures or emotional stress (Levein, 2010). RP is known to be caused by transient cessation of blood flow to the digits of the hands or feet (Cooke & Marshall, 2005). Prior studies have shown that RP is associated with various diseases such as rheumatoid arthritis, scleroderma, dematomyositis, hypertension, and migraine (Gayraud, 2007).…”

Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: A review of experimental studies

“…Raynaud's phenomenon usually is triggered by cold temperatures, or by emotions such as stress and anxiety (Cooke and Marshall, 2005). The pathological mechanisms are related to the high level of sympathetic activity (Stallworth et al, 1981;Sakakibara et al, 2002;Cooke and Marshall, 2005) and low level of CGRP expression in the local sensory fibers (Mourad and Priollet, 1997;Bunker et al, 1996). The island skin flap animal has been used to mimic the vasospastic condition (Linderoth et al, 1995 b;Qi et al, 2002).…”