Recent advances in targeting ion channels to treat chronic pain

Stevens, Edward B.; Stephens, Gary J.

doi:10.1111/bph.14215

Cited by 26 publications

(15 citation statements)

References 37 publications

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“…We then filtered only for clear-cut protein changing SNPs (missense mutations predicted deleterious by SIFT, nonsense mutations, splice site mutations, start codon mutations, and within-exon deletions and duplications), as such changes are potentially more amenable to function tests of pathogenicity; reducing from 18,106 SNPs prior to SIFT and pathogenicity analysis to 3,596 afterward. We then further filtered only for SNPs within ion channel genes, as members of this group of genes have already been implicated in Mendelian pain disorders, and testing techniques for ion channel function are well established; resulting in 28 SNPs ( Stevens and Stephens, 2018 ). For all SNPs, especially those whose rare allele frequency is < 5%, geographical and ethnic differences must be considered; rs140124801 has a rare allele frequency in EVS of 0.0051 (cohort size 6500), in gNOMAD Europeans = 0.0072 (cohort size 18,878), 1000 Genomes = 0.0048 (cohort size 2,504), and our population were Caucasian and predominantly born in the United Kingdom.…”

Section: Methodsmentioning

confidence: 99%

Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel KV6.4 Subunit

et al. 2020

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Summary By studying healthy women who do not request analgesia during their first delivery, we investigate genetic effects on labor pain. Such women have normal sensory and psychometric test results, except for significantly higher cuff pressure pain. We find an excess of heterozygotes carrying the rare allele of SNP rs140124801 in KCNG4 . The rare variant K V 6.4-Met419 has a dominant-negative effect and cannot modulate the voltage dependence of K V 2.1 inactivation because it fails to traffic to the plasma membrane. In vivo , Kcng4 (K V 6.4) expression occurs in 40% of retrograde-labeled mouse uterine sensory neurons, all of which express K V 2.1, and over 90% express the nociceptor genes Trpv1 and Scn10a . In neurons overexpressing K V 6.4-Met419, the voltage dependence of inactivation for K V 2.1 is more depolarized compared with neurons overexpressing K V 6.4. Finally, K V 6.4-Met419-overexpressing neurons have a higher action potential threshold. We conclude that K V 6.4 can influence human labor pain by modulating the excitability of uterine nociceptors.

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Section: Methodsmentioning

confidence: 99%

Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel KV6.4 Subunit

et al. 2020

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“…Chronic pain is considered as a major issue that affects the overall life quality of patient. Approximately, ~1.5 billion people are suffering with this condition globally [68] . Recently, a mouse model expressing N-type Ca v 2.2 VGCCs at the plasma membrane of peripheral somatosensory neurons via α2δ-1 accessory subunit revealed the role of these channels in pain modulation [69] , suggesting that Ca v 2.2 Ca 2+ channel may prove to be a potential drug target for novel analgesic therapies.…”

Section: Discussionmentioning

confidence: 99%

Conformational ensembles of non-peptide ω-conotoxin mimetics and Ca+2 ion binding to human voltage-gated N-type calcium channel Cav2.2

Sameera

Shah

Rashid

2020

Computational and Structural Biotechnology Journal

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“…Kim H W et al proposed that 1 Hz electroacupuncture suppressed carrageenan-induced paw inflammation via sympathetic post-ganglionic neurons, while inflammation was restrained by 120 Hz EA in connection with the sympathoadrenal medullary axis [31]. Recently, increasing evidence has shown that the analgesic effect of EA is closely related to its regulation of ion channels in sensory neurons [32,33]. Particularly, increased attention has been paid to P2X3, which has been regarded as a potential target of inflammatory pain and neuropathic pain [34,35].…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Stimulation Alleviates CFA-Induced Inflammatory Pain Via Suppressing P2X3 Expression

Xiang

Wang

Shao

et al. 2019

IJMS

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Chronic inflammatory pain is one of the most common complaints that seriously affects patients’ quality of life. Previous studies have demonstrated that the analgesic effect of electroacupuncture (EA) stimulation on inflammatory pain is related to its frequency. In this study, we focused on whether the analgesic effects of EA are related to the period of stimulation. Purinergic receptor P2X3 (P2X3) is involved in the pathological process underlying chronic inflammatory pain and neuropathic pain. We hypothesized that 100 Hz EA stimulation alleviated Freund’s complete adjuvant (CFA) induced inflammatory pain via regulating P2X3 expression in the dorsal root ganglion (DRG) and/or spinal cord dorsal horn (SCDH). We also assumed that the analgesic effect of EA might be related to the period of stimulation. We found that both short-term (three day) and long-term (14 day) 100 Hz EA stimulation effectively increased the paw withdrawal threshold (PWT) and reversed the elevation of P2X3 in the DRG and SCDH of CFA rats. However, the analgesic effects of 100 Hz EA were not dependent on the period of stimulation. Moreover, P2X3 inhibition or activation may contribute to or attenuate the analgesic effects of 100 Hz EA on CFA-induced inflammatory pain. This result indicated that EA reduced pain hypersensitivity through P2X3 modulation.

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Recent advances in targeting ion channels to treat chronic pain

Abstract: This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.

Cited by 26 publications

References 37 publications

Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel KV6.4 Subunit

Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel KV6.4 Subunit

Conformational ensembles of non-peptide ω-conotoxin mimetics and Ca+2 ion binding to human voltage-gated N-type calcium channel Cav2.2

Electroacupuncture Stimulation Alleviates CFA-Induced Inflammatory Pain Via Suppressing P2X3 Expression

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