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Paroxysmal extreme pain disorder

Vaibhav Rastogi, Devina Singh, Joseph J Mazza, Dennis Yang, Dipendra Parajuli, Steven H Yale
Flushing disorders with involvement of the gastrointestinal tract represent a heterogeneous group of conditions. In part 1 discussed were neuroendocrine tumors (NET), mast cell activation disorders (MCAD), and hyperbasophilia. In this section are covered the remaining flushing disorders which primarily or secondarily involves the gastrointestinal tract. This includes dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications...
April 12, 2018: Clinical Medicine & Research
Vaibhav Rastogi, Devina Singh, Joseph J Mazza, Dennis Yang, Dipendra Parajuli, Steven H Yale
Flushing is the subjective sensation of warmth accompanied by visible cutaneous erythema occurring throughout the body with a predilection for the face, neck, pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are superficially located and in greatest numbers. Flushing can be present in either a wet or dry form depending upon whether neural-mediated mechanisms are involved. Activation of the sympathetic nervous system results in wet flushing, accompanied by diaphoresis, due to concomitant stimulation of eccrine sweat glands...
April 12, 2018: Clinical Medicine & Research
Yue-Ming Zheng, Wan-Fu Wang, Yan-Fen Li, Yong Yu, Zhao-Bing Gao
The Nav1.7 channel represents a promising target for pain relief. In the recent decades, a number of Nav1.7 channel inhibitors have been developed. According to the effects on channel kinetics, these inhibitors could be divided into two major classes: reducing activation or enhancing inactivation. To date, however, only several inhibitors have moved forward into phase 2 clinical trials and most of them display a less than ideal analgesic efficacy, thus intensifying the controversy regarding if an ideal candidate should preferentially affect the activation or inactivation state...
April 2018: Acta Pharmacologica Sinica
See Wan Tham, Li Li, Philip Effraim, Stephen Waxman
Inherited erythromelalgia (IEM) is a well-described pain disorder caused by mutations of sodium channel Nav 1.7, a peripheral channel expressed within dorsal root ganglion and the sympathetic ganglion neurons. Clinically, IEM is characterised by paroxysmal attacks of severe pain, usually in the distal extremities, triggered by warmth or exercise. Pain is not adequately treated by existing pharmacological agents. Individuals with IEM classically cool their limbs for relief, in some cases resulting in tissue injury...
July 26, 2017: BMJ Case Reports
Dimos Kapetis, Jenny Sassone, Yang Yang, Barbara Galbardi, Markos N Xenakis, Ronald L Westra, Radek Szklarczyk, Patrick Lindsey, Catharina G Faber, Monique Gerrits, Ingemar S J Merkies, Sulayman D Dib-Hajj, Massimo Mantegazza, Stephen G Waxman, Giuseppe Lauria
BACKGROUND: Gain-of-function mutations in SCN9A gene that encodes the voltage-gated sodium channel NaV1.7 have been associated with a wide spectrum of painful syndromes in humans including inherited erythromelalgia, paroxysmal extreme pain disorder and small fibre neuropathy. These mutations change the biophysical properties of NaV1.7 channels leading to hyperexcitability of dorsal root ganglion nociceptors and pain symptoms. There is a need for better understanding of how gain-of-function mutations alter the atomic structure of Nav1...
February 24, 2017: BMC Systems Biology
Ashley Cannon, Svetlana Kurklinsky, Kimberly J Guthrie, Douglas L Riegert-Johnson
UNLABELLED: Objective. To describe the use of an advanced genetic testing technique, whole exome sequencing, to diagnose a patient and their family with a SCN9A channelopathy. Setting. Academic tertiary care center. Design. CASE REPORT: Case Report. A 61-year-old female with a history of acute facial pain, chronic pain, fibromyalgia, and constipation was found to have a gain of function SCN9A mutation by whole exome sequencing. This mutation resulted in an SCN9A channelopathy that is most consistent with a diagnosis of paroxysmal extreme pain disorder...
2016: Case Reports in Neurological Medicine
M J Eberhardt, A Leffler
Voltage-gated sodium channels (Navs) are crucial for the generation and propagation of action potentials in all excitable cells, and therefore for the function of sensory neurons as well. Preclinical research over the past 20 years identified three Nav-isoforms in sensory neurons, namely Nav1.7, Nav1.8 and Nav1.9. A specific role for the function of nociceptive neurons was postulated for each. Whereas no selective sodium channel inhibitors have been established in the clinic so far, the relevance of all three isoforms regarding the pain sensitivity in humans is currently undergoing a remarkable verification through the translation of preclinical data into clinically manifest pictures...
February 2017: Der Schmerz
Martin Hampl, Esther Eberhardt, Andrias O O'Reilly, Angelika Lampert
Mutations in the voltage-gated sodium channel Nav1.7 are linked to inherited pain syndromes such as erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD). PEPD mutations impair Nav1.7 fast inactivation and increase persistent currents. PEPD mutations also increase resurgent currents, which involve the voltage-dependent release of an open channel blocker. In contrast, IEM mutations, whenever tested, leave resurgent currents unchanged. Accordingly, the IEM deletion mutation L955 (ΔL955) fails to produce resurgent currents despite enhanced persistent currents, which have hitherto been considered a prerequisite for resurgent currents...
May 13, 2016: Scientific Reports
Michael Finley, Jason Cassaday, Tony Kreamer, Xinnian Li, Kelli Solly, Greg O'Donnell, Michelle Clements, Antonella Converso, Sean Cook, Chris Daley, Richard Kraus, Ming-Tain Lai, Mark Layton, Wei Lemaire, Donnette Staas, Jixin Wang
The NaV1.7 voltage-gated sodium channel is a highly valued target for the treatment of neuropathic pain due to its expression in pain-sensing neurons and human genetic mutations in the gene encoding NaV1.7, resulting in either loss-of-function (e.g., congenital analgesia) or gain-of-function (e.g., paroxysmal extreme pain disorder) pain phenotypes. We exploited existing technologies in a novel manner to identify selective antagonists of NaV1.7. A full-deck high-throughput screen was developed for both NaV1...
June 2016: Journal of Biomolecular Screening
David Ta Kim, Elsa Rossignol, Kinda Najem, Luis H Ospina
The SCN9A gene codes for the sodium voltage-gated channel NaV 1.7. Gain of function mutations cause pain disorders such as primary erythromelalgia, paroxysmal extreme pain disorder, and small fiber neuropathy. Loss of function mutations lead to congenital insensitivity to pain. We report the case of a 6-year-old girl with a SCN9A mutation who presented with both gain of function and loss of function phenotypes, including congenital corneal anesthesia.
October 2015: Journal of AAPOS: the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus
Marc R Suter
No abstract text is available yet for this article.
2015: Pain Management
Jennifer Koenig, Robert Werdehausen, John E Linley, Abdella M Habib, Jeffrey Vernon, Stephane Lolignier, Niels Eijkelkamp, Jing Zhao, Andrei L Okorokov, C Geoffrey Woods, John N Wood, James J Cox
The Nav1.7 voltage-gated sodium channel, encoded by SCN9A, is critical for human pain perception yet the transcriptional and post-transcriptional mechanisms that regulate this gene are still incompletely understood. Here, we describe a novel natural antisense transcript (NAT) for SCN9A that is conserved in humans and mice. The NAT has a similar tissue expression pattern to the sense gene and is alternatively spliced within dorsal root ganglia. The human and mouse NATs exist in cis with the sense gene in a tail-to-tail orientation and both share sequences that are complementary to the terminal exon of SCN9A/Scn9a...
2015: PloS One
Edward C Emery, Abdella M Habib, James J Cox, Adeline K Nicholas, Fiona M Gribble, C Geoffrey Woods, Frank Reimann
The importance of NaV1.7 (encoded by SCN9A) in the regulation of pain sensing is exemplified by the heterogeneity of clinical phenotypes associated with its mutation. Gain-of-function mutations are typically pain-causing and have been associated with inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD). IEM is usually caused by enhanced NaV1.7 channel activation, whereas mutations that alter steady-state fast inactivation often lead to PEPD. In contrast, nonfunctional mutations in SCN9A are known to underlie congenital insensitivity to pain (CIP)...
May 20, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Frank L Rice, Phillip J Albrecht, James P Wymer, Joel A Black, Ingemar Sj Merkies, Catharina G Faber, Stephen G Waxman
BACKGROUND: The skin is a morphologically complex organ that serves multiple complementary functions, including an important role in thermoregulation, which is mediated by a rich vasculature that is innervated by sympathetic and sensory endings. Two autosomal dominant disorders characterized by episodes of severe pain, inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD) have been directly linked to mutations that enhance the function of sodium channel Nav1.7. Pain attacks are accompanied by reddening of the skin in both disorders...
2015: Molecular Pain
Noboru Imai, Noriko Miyake, Yoshiaki Saito, Emiko Kobayashi, Masako Ikawa, Shinya Manaka, Masaaki Shiina, Kazuhiro Ogata, Naomichi Matsumoto
BACKGROUND: We encountered a 5-year-old girl who had short-lasting, severe, unilateral temporal headaches with ipsilateral lacrimation, nasal congestion and rhinorrhoea, and facial flushing after severe attacks. Family history revealed similar short-lasting, severe headaches in an older brother, younger sister, mother, maternal aunt, and maternal grandfather's brother. METHODS: We performed routine laboratory examinations and electrophysiological and radiological studies for three children, and whole-exome sequencing to determine the genetic causality in this family...
2015: Journal of Headache and Pain
Humberto Kluge Schroeder, Iuri Santana Neville, Daniel Ciampi de Andrade, Guilherme Alves Lepski, Manoel Jacobsen Teixeira, Kleber Paiva Duarte
BACKGROUND: Intermediate nerve neuralgia (INN) is an extremely rare craniofacial pain disorder mainly caused by neurovascular compression. CASE DESCRIPTION: We present the case of a 48-year-old female with a 20-month history of intractable paroxysmal INN on the right side. The patient described feeling paroxysmal pain in her auditory canal, pinna, deep in the jaw, and adjacent retromastoid area on the right side. She described the pain as being like a burning sensation...
2015: Surgical Neurology International
Alissa Romano, Saeed Alqahtani, James Griffith, Mohamad Z Koubeissi
Mistaking psychogenic nonepileptic paroxysmal episodes (PNEPEs) for epileptic seizures (ES) is potentially dangerous, and certain features should alert physicians to a possible PNEPE diagnosis. Psychogenic nonepileptic paroxysmal episodes due to factitious seizures carry particularly high risks of morbidity or mortality from nonindicated emergency treatment and, often, high costs in wasted medical treatment expenditures. We report a case of a 28-year-old man with PNEPEs that were misdiagnosed as ES. The patient had been on four antiseizure medications (ASMs) with therapeutic serum levels and had had multiple intubations in the past for uncontrolled episodes...
2014: Epilepsy & Behavior Case Reports
Marc R Suter, Zahurul A Bhuiyan, Cédric J Laedermann, Thierry Kuntzer, Muriel Schaller, Maurice W Stauffacher, Eliane Roulet, Hugues Abriel, Isabelle Decosterd, Christian Wider
BACKGROUND: Mutations in the SCN9A gene cause chronic pain and pain insensitivity syndromes. We aimed to study clinical, genetic, and electrophysiological features of paroxysmal extreme pain disorder (PEPD) caused by a novel SCN9A mutation. METHODS: Description of a 4-generation family suffering from PEPD with clinical, genetic and electrophysiological studies including patch clamp experiments assessing response to drug and temperature. RESULTS: The family was clinically comparable to those reported previously with the exception of a favorable effect of cold exposure and a lack of drug efficacy including with carbamazepine, a proposed treatment for PEPD...
February 2015: Anesthesiology
Brigitte A Brouwer, Ingemar S J Merkies, Monique M Gerrits, Stephen G Waxman, Janneke G J Hoeijmakers, Catharina G Faber
Pain is a frequent debilitating feature reported in peripheral neuropathies with involvement of small nerve (Aδ and C) fibers. Voltage-gated sodium channels are responsible for the generation and conduction of action potentials in the peripheral nociceptive neuronal pathway where NaV 1.7, NaV 1.8, and NaV 1.9 sodium channels (encoded by SCN9A, SCN10A, and SCN11A) are preferentially expressed. The human genetic pain conditions inherited erythromelalgia and paroxysmal extreme pain disorder were the first to be linked to gain-of-function SCN9A mutations...
June 2014: Journal of the Peripheral Nervous System: JPNS
Anamarija Meglič, Mirjana Perkovič-Benedik, Katarina Trebušak Podkrajšek, Sara Bertok
BACKGROUND: Paroxysmal extreme pain disorder (PEPD) is a rare autosomal dominant pain disorder linked to a mutation in the SCN9A gene, which encodes voltage-gated sodium channel Nav1.7. Abnormal pain sensitivity occurs because of changes in the properties of voltage-gated sodium channels. Different mutations in SCN9A and a spectrum of clinical expressions have been described. CASE-DIAGNOSIS/TREATMENT: Here we describe a 3-year-old child with a rare clinical picture of PEPD...
September 2014: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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