scholarly journals Voltage gated sodium channels as therapeutic targets for chronic pain

2019 ◽  
Vol Volume 12 ◽  
pp. 2709-2722 ◽  
Author(s):  
Renee Siu Yu Ma ◽  
Kayani Kayani ◽  
Danniella Whyte Oshodi ◽  
Aiyesha Whyte Oshodi ◽  
Nitish Nachiappan ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sodium Channels ◽  
Therapeutic Targets ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals Spider Knottin Pharmacology at Voltage-Gated Sodium Channels and Their Potential to Modulate Pain Pathways

Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 626 ◽  
Author(s):  
Yashad Dongol ◽  
Fernanda Caldas Cardoso ◽  
Richard J Lewis
Keyword(s):  
Chronic Pain ◽  
Sodium Channels ◽  
Structural Features ◽  
Voltage Gated ◽  
Subtype Selectivity ◽  
Voltage Gated Sodium Channels ◽  
Neuronal Signalling ◽  
Pain Pathways ◽  
Nav Channels ◽  
Chronic Pain Conditions

Voltage-gated sodium channels (NaVs) are a key determinant of neuronal signalling. Neurotoxins from diverse taxa that selectively activate or inhibit NaV channels have helped unravel the role of NaV channels in diseases, including chronic pain. Spider venoms contain the most diverse array of inhibitor cystine knot (ICK) toxins (knottins). This review provides an overview on how spider knottins modulate NaV channels and describes the structural features and molecular determinants that influence their affinity and subtype selectivity. Genetic and functional evidence support a major involvement of NaV subtypes in various chronic pain conditions. The exquisite inhibitory properties of spider knottins over key NaV subtypes make them the best lead molecules for the development of novel analgesics to treat chronic pain.

scholarly journals Voltage-Gated Sodium Channels: Therapeutic Targets for Pain

Pain Medicine ◽  
2009 ◽  
Vol 10 (7) ◽  
pp. 1260-1269 ◽  
Author(s):  
Sulayman D. Dib-Hajj ◽  
Joel A. Black ◽  
Stephen G. Waxman
Keyword(s):  
Sodium Channels ◽  
Therapeutic Targets ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals The Role of Voltage-Gated Sodium Channels in Pain Signaling

2019 ◽  
Vol 99 (2) ◽  
pp. 1079-1151 ◽  
Author(s):  
David L. Bennett ◽  
Alex J. Clark ◽  
Jianying Huang ◽  
Stephen G. Waxman ◽  
Sulayman D. Dib-Hajj
Keyword(s):  
Chronic Pain ◽  
Sodium Channels ◽  
Sensory Neuron ◽  
Sensory Neurons ◽  
Expression Patterns ◽  
Sensory Transduction ◽  
Gene Variants ◽  
Sensory Stimuli ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

Acute pain signaling has a key protective role and is highly evolutionarily conserved. Chronic pain, however, is maladaptive, occurring as a consequence of injury and disease, and is associated with sensitization of the somatosensory nervous system. Primary sensory neurons are involved in both of these processes, and the recent advances in understanding sensory transduction and human genetics are the focus of this review. Voltage-gated sodium channels (VGSCs) are important determinants of sensory neuron excitability: they are essential for the initial transduction of sensory stimuli, the electrogenesis of the action potential, and neurotransmitter release from sensory neuron terminals. Nav1.1, Nav1.6, Nav1.7, Nav1.8, and Nav1.9 are all expressed by adult sensory neurons. The biophysical characteristics of these channels, as well as their unique expression patterns within subtypes of sensory neurons, define their functional role in pain signaling. Changes in the expression of VGSCs, as well as posttranslational modifications, contribute to the sensitization of sensory neurons in chronic pain states. Furthermore, gene variants in Nav1.7, Nav1.8, and Nav1.9 have now been linked to human Mendelian pain disorders and more recently to common pain disorders such as small-fiber neuropathy. Chronic pain affects one in five of the general population. Given the poor efficacy of current analgesics, the selective expression of particular VGSCs in sensory neurons makes these attractive targets for drug discovery. The increasing availability of gene sequencing, combined with structural modeling and electrophysiological analysis of gene variants, also provides the opportunity to better target existing therapies in a personalized manner.

Voltage-gated sodium channels as therapeutic targets

2000 ◽  
Vol 5 (11) ◽  
pp. 506-520 ◽  
Author(s):  
Jeffrey J. Clare ◽  
Simon N. Tate ◽  
Malcolm Nobbs ◽  
Mike A. Romanos
Keyword(s):  
Sodium Channels ◽  
Therapeutic Targets ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders

2010 ◽  
Vol 9 (4) ◽  
pp. 413-424 ◽  
Author(s):  
Massimo Mantegazza ◽  
Giulia Curia ◽  
Giuseppe Biagini ◽  
David S Ragsdale ◽  
Massimo Avoli
Keyword(s):  
Sodium Channels ◽  
Neurological Disorders ◽  
Therapeutic Targets ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

Voltage-Gated Sodium Channels as Therapeutic Targets

2012 ◽  
pp. 63-122 ◽  
Author(s):  
Joshua S. Wingerd ◽  
Irina Vetter ◽  
Richard J. Lewis
Keyword(s):  
Sodium Channels ◽  
Therapeutic Targets ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels
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