Erythromelalgia
NAV1.7 Voltage-Gated Sodium Channel
Arteriovenous Anastomosis
Voltage-Gated Sodium Channel beta-2 Subunit
Pain Insensitivity, Congenital
Sodium Channels
Voltage-Gated Sodium Channel beta-4 Subunit
Ganglia, Spinal
Impaired skin vasomotor reflexes in patients with erythromelalgia. (1/53)
Erythromelalgia (EM) is a chronic disorder characterized by intermittent burning pain, warmth and erythema of the extremities. Increasing the local temperature and dependency of the affected limb(s) precipitates the symptoms, whereas direct cooling and elevation of the limb(s) can provide partial relief. Our previous findings showed that patients with EM have enhanced cutaneous vascular tone at rest and during stimulation, which may be due to an increase in sympathetic neural activity. To test this, we measured skin vasoconstrictor responses to contralateral arm cold challenge (CC) and inspiratory gasp (IG) using laser Doppler flowmetry at the toe pulp and fingertip. These areas were chosen because of their dense sympathetic innervation. An index of the vasoconstrictor response (between 0 and 1) was calculated from the change in skin perfusion from baseline following CC and IG. In control subjects, vasoconstrictor responses to CC at the toe and fingertip were both 0. 70+/-0.02 (mean+/-S.E.M.), which were significantly greater (P<0. 001) than corresponding values in patients with EM (0.37+/-0.04 and 0.45+/-0.04 respectively). Similarly, vasoconstrictor responses to IG were significantly greater (P<0.001) at the toe and fingertip in control subjects (0.70+/-0.03 and 0.70+/-0.02 respectively) compared with values in EM patients (0.27+/-0.03 and 0.45+/-0.15 respectively). These data show that, in contrast with control subjects, patients with EM have diminished sympathetic vasoconstrictor responses to both CC and IG. Denervation supersensitivity may play a part by increasing vasoconstrictor responses to circulating catecholamines, leading to a reduction in skin blood flow. Therefore an interplay between neural and vasoactive agents may be involved in the pathophysiology of EM. (+info)Microvascular arteriovenous shunting is a probable pathogenetic mechanism in erythromelalgia. (2/53)
Erythromelalgia is a condition consisting of red, warm, and burning painful extremities. Symptoms are relieved by cold and aggravated by heat. A wide variety of etiologic conditions can cause erythromelalgia, but one common pathogenetic mechanism, microvascular arteriovenous shunting, has been hypothesized. The aim of this study was to test this hypothesis. Quantification of skin microvascular perfusion using laser Doppler perfusion imaging and skin temperature at rest and after central body heating was performed in 14 patients with erythromelalgia and 11 controls. Attacks of erythromelalgia were induced in eight patients after heat provocation. In the plantar region of the foot, the location of numerous anatomical arteriovenous shunts, these patients significantly increased the skin perfusion as compared with asymptomatic patients with erythromelalgia and controls. In the dorsal region with few arteriovenous shunts no significant differences between the groups were demonstrated. The results show a relation between clinical symptoms and increased perfusion in the region of numerous anatomical arteriovenous shunts, and support the hypothesis of increased thermoregulatory arteriovenous shunt flow during attacks in primary erythromelalgia. (+info)Erythromelalgia--a thrombotic complication in chronic myeloproliferative disorders. (3/53)
Erythromelalgia is a very specific, thrombotic syndrome related with thrombocythemia that may occur during the course of chronic myeloproliferative disorders (MPD), especially polycythemia vera (PV) and essential thrombocythemia (ET). This poorly understood clinical syndrome is characterized by red, congested distal extremities and painful burning sensations, usually confined to the ball of the foot and one or more toes or fingers. If left untreated, it may progress towards acrocyanosis and even peripheral gangrene. Sometimes, it may precede the diagnosis of MPD by months or years. The pathophysiological aspects of erythromelalgia as well as its differentiation with erythermalgia have been reviewed in this study. (+info)Myeloproliferative disorders--neurological complications. (4/53)
Primary myeloproliferative disorders (MPD) are often associated with hemostasis abnormalities, which may cause many thrombotic or hemorrhagic complications during the course of the disease. Clinical consequences following abnormal hemostatic conditions include various neurological manifestations. It is extremely difficult to predict and evaluate the risk and chance, that MPD patients will develop neurological symptoms. The up-to-date background of pathological thrombocytosis, as well as the neurological aspects of abnormal hemostasis during the course of myeloproliferative disorders have been reviewed in this study. (+info)The primary erythermalgia-susceptibility gene is located on chromosome 2q31-32. (5/53)
Primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm, and painful hands and/or feet. The symptoms are generally refractory to treatment and persist throughout life. Five kindreds with multiple cases of primary erythermalgia were identified, and the largest was subjected to a genomewide search. We detected strong evidence for linkage of the primary erythermalgia locus to markers from chromosome 2q. The highest LOD score (Z) was obtained with D2S2330 (Z(max) = 6.51). Analysis of recombination events identified D2S2370 and D2S1776 as flanking markers, on chromosome 2q31-32. This defines a critical interval of 7.94 cM that harbors the primary erythermalgia gene. Affected members within the additional families also shared a common haplotype on chromosome 2q31-32, supporting our linkage results. Identification of the primary erythermalgia gene will allow a better clinical classification of this pleomorphic group of disorders. (+info)Impaired neurogenic control of skin perfusion in erythromelalgia. (6/53)
Erythromelalgia is a clinical diagnosis characterized by erythema, increased temperature and burning pain in acral skin. The pain is relieved by cooling and aggravated by warming. The symptoms have been hypothesized to be caused by skin hypoxia due to increased arteriovenous shunting. We examined skin microvascular perfusion in response to vasoconstrictory and vasodilatory stimuli, to characterize local and central neurogenic reflexes as well as vascular smooth muscle and vascular endothelial function, using laser Doppler perfusion measurements in 14 patients with primary erythromelalgia and healthy control persons. Skin perfusion preceding provocative stimuli was significantly reduced in patients with erythromelalgia (p < 0.01). The laser Doppler flowmetry signal after sympathetic stimulation of reflexes mediated through the central nervous system, was significantly diminished in patients with erythromelalgia as compared with healthy controls (Valsalva's maneuver p < 0.01; contralateral cooling test p < 0.05). Local neurogenic vasoconstrictor (venous cuff occlusion and dependency of the extremity) and vasodilator reflexes (local heating of the skin), as well as tests for vascular smooth muscle and vascular endothelial function (postocclusive hyperemic response) were maintained. These results indicate that postganglionic sympathetic dysfunction and denervation hypersensitivity may play a pathogenetic role in primary erythromelalgia, whereas local neurogenic as well as endothelial function is unaffected. (+info)Erythromelalgia: an endothelial disorder responsive to sodium nitroprusside. (7/53)
Erythromelalgia is an unusual syndrome of painful vasodilatation. Aetiopathology is probably different in children and adults. Presentation can be severe and associated with hypertension. Dramatic benefit from infused nitroprusside suggests the disorder could represent a dysfunctional endothelium. (+info)Reduced skin capillary density during attacks of erythromelalgia implies arteriovenous shunting as pathogenetic mechanism. (8/53)
Erythromelalgia is characterized by burning pain, erythema, and increased temperature in acral skin. The pain is aggravated by warming and relieved by cooling. Increased microvascular arteriovenous shunting in deep dermal plexa has been hypothesized as the pathogenetic mechanism of pain in affected skin, inducing hypoxia during pain attacks. The aim of this study was to quantify skin capillary density in erythromelalgic patients before and after heat provocation, as increased skin temperature should increase the need for nutritive blood supply by the capillaries. Fourteen patients and 10 healthy control subjects were studied using an enhanced technique of computer-assisted analysis of capillary bed morphology and temperature measurements before and after central body heating. The increase in acral skin temperature was significantly higher (p < 0.05) in the eight patients where symptoms were induced after heat provocation, compared to asymptomatic patients and healthy control subjects. The number of visible capillaries in a field of view (1.7 mm2) decreased significantly (p = 0.01) in erythromelalgia patients from 105 (62-137) (median with total range) to 89 (49-118) after warming in areas with numerous arteriovenous anastomoses (nail bed region). In symptomatic patients an even more significant reduction was observed (p = 0.01). The capillary size was also significantly reduced (p < 0.05) from 41.0 (31.5-50.5) (arbitrary units) to 37.3 (33.0-46.0) in symptomatic patients. The change in capillary density in the nail bed area was significantly larger in erythromelalgia patients -17 (-49 to 39) compared to controls 0 (-47 to 13) (p < 0.05), and in symptomatic patients -19 (-49 to -12) compared to asymptomatic patients -8 (-48 to 39) (p < 0.05) and controls (p < 0.01). The reduced skin capillary density after heating is compatible with increased microvascular arteriovenous shunting of blood and a corresponding relative deficit in nutritive perfusion (steal phenomenon) with skin hypoxia, causing the symptoms in erythromelalgia. (+info)Erythromelalgia is a rare vascular disorder characterized by recurrent episodes of burning pain, erythema (redness), and increased temperature in the extremities, typically the hands and feet. The symptoms are caused by abnormal dilatation (widening) of the small blood vessels, leading to increased blood flow and oxygen supply to the affected areas. This condition can be primary (idiopathic), meaning it occurs without any known underlying cause, or secondary, resulting from another medical condition such as peripheral neuropathy, myeloproliferative disorders, or connective tissue diseases. Treatment for erythromelalgia aims to alleviate symptoms and may include medications that help narrow blood vessels, such as aspirin, calcium channel blockers, or topical capsaicin cream.
NAV1.7, also known as SCN9A, is a gene that encodes for the α subunit of a voltage-gated sodium channel. This specific sodium channel, referred to as the Nav1.7 voltage-gated sodium channel, plays a crucial role in the initiation and propagation of action potentials in neurons, particularly in peripheral nerves.
The Nav1.7 channel is primarily responsible for generating the rapid upstroke of the action potential, which is essential for nerve impulse transmission. It exhibits unique biophysical properties, such as slow activation, fast inactivation, and rapid repriming, making it highly sensitive to small changes in membrane voltage. This sensitivity allows Nav1.7 channels to function as threshold channels, selectively amplifying subthreshold depolarizations and contributing to the generation of action potentials.
Dysfunction in the Nav1.7 channel has been implicated in various pain-related disorders. Gain-of-function mutations in the SCN9A gene can lead to chronic pain conditions, such as inherited erythromelalgia and paroxysmal extreme pain disorder. In contrast, loss-of-function mutations have been associated with congenital insensitivity to pain, a rare condition characterized by the inability to experience pain. Thus, Nav1.7 channels are considered promising targets for the development of novel analgesic drugs.
An arteriovenous (AV) anastomosis is a connection or short channel between an artery and a vein that bypasses the capillary bed. In a normal physiological condition, blood flows from the arteries to the capillaries, where oxygen and nutrients are exchanged with the surrounding tissues, and then drains into veins. However, in an AV anastomosis, blood flows directly from the artery to the vein without passing through the capillary network.
AV anastomoses can occur naturally or be created surgically for various medical purposes. For example, they may be created during bypass surgery to reroute blood flow around a blocked or damaged vessel. In some cases, AV anastomoses may also develop as a result of certain medical conditions, such as cirrhosis or arteriovenous malformations (AVMs). AVMs are abnormal connections between arteries and veins that can lead to the formation of an AV anastomosis.
It is important to note that while AV anastomoses can be beneficial in certain medical situations, they can also have negative consequences if they occur inappropriately or become too large. For example, excessive AV anastomoses can lead to high-flow shunts, which can cause tissue damage and other complications.
The voltage-gated sodium channel β-2 subunit, also known as SCN3B or NaVβ2, is a regulatory protein that associates with the pore-forming α-subunit of voltage-gated sodium channels. These channels play crucial roles in generating and propagating action potentials in excitable cells such as neurons and muscle cells.
The β-2 subunit is a member of the immunoglobulin superfamily, containing an extracellular immunoglobulin-like domain, a transmembrane segment, and a short intracellular tail. The primary function of the β-2 subunit is to modulate the kinetic properties and plasma membrane expression of the sodium channel complex. It can influence the voltage dependence, activation, and inactivation of sodium currents, as well as the susceptibility to channel blockers.
The β-2 subunit also interacts with other cell adhesion molecules and extracellular matrix proteins, which may contribute to the proper localization and clustering of sodium channels at nodes of Ranvier in myelinated neurons or at the neuromuscular junction. Mutations in the SCN3B gene have been associated with various neurological disorders, including epilepsy and periodic paralyses.
Congenital pain insensitivity, also known as congenital analgesia, is a rare genetic disorder characterized by the absence of ability to feel pain due to the malfunction or lack of functioning nociceptors - the nerve cells that transmit painful stimuli to the brain. It is typically caused by mutations in the SCN9A gene, which encodes a sodium channel necessary for the function of nociceptors.
Individuals with congenital pain insensitivity may not feel any pain from injuries or other sources of harm, and as a result, they are at risk for serious injury or even death due to lack of protective responses to painful stimuli. They may also have an increased risk of developing recurrent infections and self-mutilation behaviors.
It is important to note that while these individuals do not feel pain, they can still experience other sensory inputs such as touch, temperature, and pressure. Congenital pain insensitivity is a complex medical condition that requires careful management and monitoring by healthcare professionals.
Sodium channels are specialized protein structures that are embedded in the membranes of excitable cells, such as nerve and muscle cells. They play a crucial role in the generation and transmission of electrical signals in these cells. Sodium channels are responsible for the rapid influx of sodium ions into the cell during the initial phase of an action potential, which is the electrical signal that travels along the membrane of a neuron or muscle fiber. This sudden influx of sodium ions causes the membrane potential to rapidly reverse, leading to the depolarization of the cell. After the action potential, the sodium channels close and become inactivated, preventing further entry of sodium ions and helping to restore the resting membrane potential.
Sodium channels are composed of a large alpha subunit and one or two smaller beta subunits. The alpha subunit forms the ion-conducting pore, while the beta subunits play a role in modulating the function and stability of the channel. Mutations in sodium channel genes have been associated with various inherited diseases, including certain forms of epilepsy, cardiac arrhythmias, and muscle disorders.
The voltage-gated sodium channel β-4 subunit, also known as SCN4B, is a protein that forms part of the voltage-gated sodium channel complex in excitable cells such as neurons and muscle cells. The channel complex is responsible for the rapid influx of sodium ions into the cell during the initiation and propagation of action potentials.
The β-4 subunit is one of several accessory proteins that associate with the pore-forming α-subunit to modulate the function of the channel. Specifically, the β-4 subunit has been shown to regulate the kinetics and voltage dependence of sodium channel activation and inactivation, as well as the expression and trafficking of the channel complex to the cell membrane.
Mutations in the SCN4B gene, which encodes the β-4 subunit, have been associated with various forms of inherited peripheral nerve hyperexcitability disorders, such as paramyotonia congenita and hyperkalemic periodic paralysis. These disorders are characterized by muscle stiffness, cramping, and weakness in response to cold or exercise, and are thought to result from abnormalities in sodium channel function.
Skin temperature is the measure of heat emitted by the skin, which can be an indicator of the body's core temperature. It is typically lower than the body's internal temperature and varies depending on factors such as environmental temperature, blood flow, and physical activity. Skin temperature is often used as a vital sign in medical settings and can be measured using various methods, including thermal scanners, digital thermometers, or mercury thermometers. Changes in skin temperature may also be associated with certain medical conditions, such as inflammation, infection, or nerve damage.
Spinal ganglia, also known as dorsal root ganglia, are clusters of nerve cell bodies located in the peripheral nervous system. They are situated along the length of the spinal cord and are responsible for transmitting sensory information from the body to the brain. Each spinal ganglion contains numerous neurons, or nerve cells, with long processes called axons that extend into the periphery and innervate various tissues and organs. The cell bodies within the spinal ganglia receive sensory input from these axons and transmit this information to the central nervous system via the dorsal roots of the spinal nerves. This allows the brain to interpret and respond to a wide range of sensory stimuli, including touch, temperature, pain, and proprioception (the sense of the position and movement of one's body).
Erythromelalgia