| ¿Están los canales de sodio dependientes de voltaje de la raíz del ganglio dorsal involucrados en el desarrollo del dolor neuropático? |
Are voltage-gated sodium channels on the dorsal root ganglion involved in the development of neuropathic pain?
Wang W, Gu J, Li YQ, Tao YX.
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Mol Pain. 2011 Feb 23;7:16.
Abstract
Neuropathic pain is a common clinical condition. Current treatments are often inadequate, ineffective, or produce potentially severe adverse effects. Understanding the mechanisms that underlie the development and maintenance of neuropathic pain will be helpful in identifying new therapeutic targets and developing effective strategies for the prevention and/or treatment of this disorder. The genesis of neuropathic pain is reliant, at least in part, on abnormal spontaneous activity within sensory neurons. Therefore, voltage-gated sodium channels, which are essential for the generation and conduction of action potentials, are potential targets for treating neuropathic pain. However, preclinical studies have shown unexpected results because most pain-associated voltage-gated channels in the dorsal root ganglion are down-regulated after peripheral nerve injury. The role of dorsal root ganglion voltage-gated channels in neuropathic pain is still unclear. In this report, we describe the expression and distribution of voltage-gated sodium channels in the dorsal root ganglion. We also review evidence regarding changes in their expression under neuropathic pain conditions and their roles in behavioral responses in a variety of neuropathic pain models. We finally discuss their potential involvement in neuropathic pain
http://www.molecularpain.com/content/pdf/1744-8069-7-16.pdf
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| Canales de sodio dependientes de voltaje: Objetivos terapéuticos del dolor |
Voltage-Gated Sodium Channels: Therapeutic Targets for Pain
Sulayman D. Dib-Hajj, PhD, Joel A. Black, PhD, and Stephen G. Waxman, MD, PhD
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut, and Rehabilitation Research Center, Veterans Administration Connecticut Healthcare System, West Haven, Connecticut, USA
PAIN MEDICINE Volume 10 · Number 7 · 2009
Objective. To provide an overview of the role of voltage-gated sodium channels in pathophysiology of acquired and inherited pain states, and of recent developments that validate these channels as therapeutic targets for treating chronic pain. Background. Neuropathic and inflammatory pain conditions are major medical needs worldwide with only partial or low efficacy treatment options currently available. An important role of voltage-gated sodium channels in many different pain states has been established in animal models and, empirically, in humans, where sodium channel blockers partially ameliorate pain. Animal studies have causally linked changes in sodium channel expression and modulation that alter channel gating properties or current density in nociceptor neurons to different pain states. Biophysical and pharmacological studies have identified the sodium channel isoforms Nav1.3, Nav1.7, Nav1.8, and Nav1.9 as particularly important in the pathophysiology of different pain syndromes. Recently, gain-of-function mutations in SCN9A, the gene which encodes Nav1.7, have been linked to two human-inherited pain syndromes, inherited erythromelalgia and paroxysmal extreme pain disorder, while loss-of-function mutations in SCN9A have been linked to complete insensitivity to pain. Studies on firing properties of sensory neurons of dorsal root ganglia demonstrate that the effects of gain-of-function mutations in Nav1.7 on the excitability of these neurons depend on the presence of Nav1.8, which suggests a similar physiological interaction of these two channels in humans carrying the Nav1.7 pain mutation. Conclusions. These studies suggest that isoform-specific blockers of these channels or targeting of their modulators may provide novel approaches to treatment of pain.
Key Words. Chronic Pain; Diabetic Neuropathy; Inflammation; Pain Disorder; Persistent Pain
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| Los papeles de los canales de sodio en la nocicepción: implicaciones para los mecanismos del dolor |
The roles of sodium channels in nociception: Implications for mechanisms of pain.
Cummins TR, Sheets PL, Waxman SG.
Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, United States. trcummin@iupui.edu <trcummin@iupui.edu>
Pain. 2007 Oct;131(3):243-57. Epub 2007 Sep 4.
Abstract
Understanding the role of voltage-gated sodium channels in nociception may provide important insights into pain mechanisms. Voltage-gated sodium channels are critically important for electrogenesis and nerve impulse conduction, and a target for important clinically relevant analgesics such as lidocaine. Furthermore, within the last decade studies have shown that certain sodium channel isoforms are predominantly expressed in peripheral sensory neurons associated with pain sensation, and that the expression and functional properties of voltage-gated sodium channels in peripheral sensory neurons can be dynamically regulated following axonal injury or peripheral inflammation. These data suggest that specific voltage-gated sodium channels may play crucial roles in nociception. Experiments with transgenic mice lines have clearly implicated Na(v)1.7, Na(v)1.8 and Na(v)1.9 in inflammatory, and possibly neuropathic, pain. However the most convincing and perhaps most exciting results regarding the role of voltage-gated sodium channels have come out recently from studies on human inherited disorders of nociception. Point mutations in Na(v)1.7 have been identified in patients with two distinct autosomal dominant severe chronic pain syndromes. Electrophysiological experiments indicate that these pain-associated mutations cause small yet significant changes in the gating properties of voltage-gated sodium channels that are likely to contribute substantially to the development of chronic pain. Equally exciting, recent studies indicate that recessive mutations in Na(v)1.7 that eliminate functional current can result in an apparent complete, and possibly specific, indifference to pain in humans, suggesting that isoform specific blockers could be very effective in treating pain. In this review we will examine what is known about the roles of voltage-gated sodium channels in nociception
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