Calcitonin gene-related peptide, endothelin-1, the cutaneous microvasculature and Raynaud's phenomenon

Bunker, C.B.; Goldsmith, P. C.; Leslie, Tabi A.; Hayes, N.A.; Foreman, J. C.; Dowd, Pauline M.

doi:10.1111/j.1365-2133.1996.tb16221.x

Cited by 43 publications

(23 citation statements)

References 37 publications

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“…Bunker et al showed the loss of CGRP containing nerve fibers (5), with decreased skin blood flow response to CGRP when fingers were exposed to cold (using an environmental chamber; Ref. 4). In the present study, the use of local anesthesia on the dorsum of the finger partially restored the transient vasodilation in participants with primary RP when cooling locally at 15°C.…”

Section: Discussionsupporting

confidence: 54%

Impaired transient vasodilation and increased vasoconstriction to digital local cooling in primary Raynaud's phenomenon

Roustit

Blaise

Millet

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Raynaud's phenomenon (RP) is defined as episodic ischemia of the extremities in response to cold. Although the structure of skin capillaries is normal in primary RP, some data suggest impairment of microvascular function. We aimed at testing whether digital skin blood flow was lower in RP than in controls while cooling locally. We further evaluated the contribution of sensory nerves in the response. We recruited 21 patients with primary RP and 20 healthy volunteers matched on age and gender. After a 10-min baseline at 33°C, skin temperature was cooled at 15 or 24°C during 30 min on the forearm and the finger while monitoring perfusion with a custom-design laser Doppler flowmetry probe. Perfusion was also assessed after topical anesthesia. Blood flow was expressed as cutaneous vascular conductance (CVC). Data were subsequently expressed as area above the curve (AAC0 -30) of the percentage decrease from baseline CVC (%BL). CVC on the dorsum of the finger was lower in RP patients compared with controls at 15°C (AAC0 -30 were 106,237.2 and 69,544.3%BL·s, respectively; P ϭ 0.02) and at 24°C (AAC0 -30 were 86,915 and 57,598%BL·s, respectively; P ϭ 0.04) whereas we observed no significant difference on the finger pad and the forearm. Topical anesthesia increased CVC in patients with RP (P ϭ 0.05), whereas it did not affect reactivity in controls (P ϭ 0.86). Our study shows exaggerated skin microvascular vasoconstriction to local cooling on the dorsum of the finger in primary RP compared with controls. Part of this abnormal response in primary RP depends on sensitive nerves. microcirculation; skin blood flow FIRST DESCRIBED BY MAURICE RAYNAUD in 1862 (25), Raynaud's phenomenon (RP) is defined as episodic ischemia of the extremities in response to cold or emotional stimuli, often accompanied by pain. It presents clinically as pallor, cyanosis, and often rubor of the skin. Pallor indicates vasospasm and decreased blood flow, and cyanosis is a sign of deoxygenation of the static venous blood, while rubor implies reactive hyperemia (2). RP can be primary (i.e., idiopathic) or secondary to a connective tissue disease. The pathophysiology of primary RP is multifactorial and complex, with both vascular and neural abnormalities (7,15). Although available evidence suggests that microvascular function is impaired in primary RP, the exact mechanism of such dysfunction remains poorly understood.

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Section: Discussionsupporting

confidence: 54%

Impaired transient vasodilation and increased vasoconstriction to digital local cooling in primary Raynaud's phenomenon

Roustit

Blaise

Millet

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…86 Bunker et al have argued that, in normal subjects, the CGRP-containing digital cutaneous nerves are stimulated in response to cold and release CGRP which produces dilation, and helps to counteract cold-induced vasoconstriction. 87 Thus, they maintain that CGRP is a major contributor to cold-induced vasodilation. They further propose that ET-1, which others have shown is found released in response to cooling (see above), not only produces local constriction, but activates the CGRP-containing sensory nerves to produce vasodilation.…”

Section: Calcitonin Gene-related Peptide (Cgrp)mentioning

confidence: 99%

Mechanisms of Raynaud’s disease

2005

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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.

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“…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).…”

Section: 15mentioning

confidence: 99%

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

Linderoth

Foreman

2008

Autonomic Neuroscience

159

106

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Spinal cord stimulation (SCS) is a widely used clinical technique to treat ischemic pain in peripheral, cardiac and cerebral vascular diseases. The use of this treatment advanced rapidly during the late 80's and 90's, particularly in Europe. Although the clinical benefits of SCS are clear and the success rate remains high, the mechanisms are not yet completely understood. SCS at lumbar spinal segments (L2-L3) produces vasodilation in the lower limbs and feet which is mediated by antidromic activation of sensory fibers and decreased sympathetic outflow. SCS at thoracic spinal segments (T1-T2) induces several benefits including pain relief, reduction in both frequency and severity of angina attacks, and reduced short-acting nitrate intake. The benefits to the heart are not likely due to an increase, or redistribution of local blood flow, rather, they are associated with SCS-induced myocardial protection and normalization of the intrinsic cardiac nervous system. At somewhat lower cervical levels (C3-C6), SCS induces increased blood flow in the upper extremities. SCS at the upper cervical spinal segments (C1-C2) increased cerebral blood flow, which is associated with a decrease in sympathetic activity, an increase in vasomotor center activity and a release of neurohumoral factors. This review will summarize the basic science studies that have contributed to our understanding about mechanisms through which SCS produces beneficial effects when used in the treatment of vascular diseases. Furthermore, this review will particularly focus on the antidromic mechanisms of SCS-induced vasodilation in the lower limbs and feet.

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Calcitonin gene-related peptide, endothelin-1, the cutaneous microvasculature and Raynaud's phenomenon

Cited by 43 publications

References 37 publications

Impaired transient vasodilation and increased vasoconstriction to digital local cooling in primary Raynaud's phenomenon

Impaired transient vasodilation and increased vasoconstriction to digital local cooling in primary Raynaud's phenomenon

Mechanisms of Raynaud’s disease

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

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