疼痛

痛みは通常、実際もしくは潜在的な組織損傷に関連する不快な感覚的および感情的な経験として定義され、傷害を防ぐ重要なメカニズムとして役立っています。痛みの感覚は、末梢からの入力に対する脳の応答として生じます。傷害、病気または身体の損傷のために現れる電気的および化学的変化は、多数のイオンチャネルによって中枢へ伝達されます。これらに関わるイオンチャネルの役割には、刺激を開始するもの、電気的に伝導するものと、シナプスを介して化学的に伝達するものなどがあります。

 

疼痛には、神経因性(神経損傷)疼痛と侵害受容性(組織)痛の2つの基本的なタイプがあります。

神経因性疼痛は、神経系の原発損傷または機能不全により引き起こされ、損傷組織の治癒後も長く持続し、慢性疼痛に変わる可能性があります。侵害受容性疼痛は、侵害受容器が損傷または炎症を起こした組織によって刺激された場合に生じます。痛みは通常時間が限られており、身体を保護する目的で伝えられます。

 

痛みに関与するイオンチャネルについては多くの事例があり、それぞれのイオンチャネルが異なる役割を果たすことが示されてきました。 電位依存性Na+チャネルは、求心性神経線維に沿った伝導にとって重要であり、電位依存性Ca2+チャネルは、シナプス間隙における神経伝達物質の放出に重要な役割を果たします。またTransient receptor potential チャネル(TRP)、Acid-sensingイオンチャネル(ASIC)、グルタミン酸受容体(KA、NMDAおよびAMPAリガンド依存性イオンチャネル)などは、皮下に存在する自由神経終末での一次侵害受容応答に関与します。

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痛覚の感受および伝達に関与するイオンチャネル:

 

Key Pain Ion Channels

Nav1.1, 1.6, 1.7 & 1.8 (1.3 after injury)
Cav1.2
TRP
P2X
NMDA, AMPA and KA
ASIC1-3

 

 


Nav1.1, 1.3, 1,4, 1.6, 1.7 & 1.8

Posters

  • 詳細 Biophysical and pharmacological characterization of multiple Nav subtypes on Qube
    Year: 2016 First author: Lindqvist et Al
  • 詳細 CHO-hNav1.7 assay on Qube pharmacology, biophysical characterization and the effect of internal fluoride
    Year: 2017 First author: Sauter et al., 2017
  • 詳細 Sophion analyzer as a tool for biophysical and pharmacological characterization of eight Nav subtypes evaluated in parallel on Qube
    Year: 2016 First author: Korsgaard et al., 2016
  • 詳細 Biophysical and pharmacological profiling of multiple Nav subtypes on QPatch HT
    Year: 2016 First author: Lindqvist et al., 2016
  • 詳細 “Clip Detecting” with series resistance compensation using an automated patch clamp system
    Year: 2012 First author: Løjkner et al., 2012
  • A small molecule activator of Nav1.1 channels increases fast-spiking interneuron excitability and GABAergic transmission in vitro and has anti-convulsive effects in vivo
    Year: 2017 First author: K Frederiksen

Papers

  • 詳細 Selective NaV1.7 Antagonists with Long Residence Time Show Improved Efficacy against Inflammatory and Neuropathic Pain
    Year: 2018 First author: Bankar et Al.
  • 詳細 The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/− mice
    Year: 2017
  • 詳細 High-Throughput Screening of Nav1.7 Modulators Using a Giga-Seal Automated Patch Clamp Instrument
    Year: 2016 First author: Chambers et al., 2016
  • 詳細 Identification and Electrophysiological Evaluation of 2-Methylbenzamide Derivatives as Nav1.1 Modulators
    Year: 2015 First author: Crestey et al., 2015
  • 詳細 Characterization of Endogenous Sodium Channels in the ND7-23 Neuroblastoma Cell Line: Implications for Use as a Heterologous Ion Channel Expression System Suitable for Automated Patch Clamp Screening
    Year: 2016 First author: Rogers et al., 2016
  • 詳細 Engineering Highly Potent and Selective Microproteins Against Nav1.7 Sodium Channel for Treatment of Pain
    Year: 2016 First author: Shcherbatko et al., 2016
  • 詳細 Rational engineering defines a molecular switch that is essential for activity of spider-venom peptides against the analgesics target Nav1.7
    Year: 2015 First author: Klint et al., 2015
  • 詳細 Using automated patch clamp electrophysiology platforms in pain-related ion channel research: insights from industry and academia
    Year: 2017 First author: Bell

Reports

  • Nav1.1 currents on Qube
    Year: 2018 First author: Klint et Al.
  • 詳細 High throughput screening for mode-of-action on Nav1.4
    Year: 2017 First author: Sauter

Cav1.2

Posters

  • 詳細 Qube as a tool for assay optimization of CiPA cells and protocols by using multiple IC, EC solutions and hERG, Nav1.5 and Cav1.2 on the same QChip
    Year: 2016 First author: Schupp et al., 2016
  • 詳細 Exploring stem cell-derived cardiomyocytes with automated patch clamp techniques
    Year: 2012 First author: Schrøder et al., 2012

Papers

  • 詳細 A new classifier-based strategy for in-silico ion-channel cardiac drug safety assessment
    Year: 2015 First author: Mistry et al., 2015
  • 詳細 Screening system for drug-induced arrhythmogenic risk combining a patch clamp and heart simulator
    Year: 2015 First author: Okada et al., 2015
  • 詳細 MICE Models: Superior to the HERG Model in Predicting Torsade de Pointes
    Year: 2013 First author: Kramer et al., 2013

Reports

  • 詳細 hCav1.2 recordings on Qube 384 using step, train and CiPA protocols
    Year: 2018 First author: Schupp
  • 詳細 Cav1.2 on Qube 384
    Year: 2017 First author: Schupp, M
  • 詳細 CHO Cav1.2 on QPatch (ChanTest)
    Year: 2011 First author: Friis et al., 2011
  • 詳細 Cor.At cells embryonic stem cell derived cardiomyocytes on QPatch
    Year: 2009 First author: Schrøder et al., 2009

TRP

Posters

  • 詳細 TRP’ing in multi-hole mode
    Year: 2010 First author: Jacobsen et al., 2010

Papers

  • 詳細 The development of automated patch clamp assays for canonical transient receptor potential channels TRPC3, 6, and 7
    Year: 2014 First author: McPate et Al.
  • 詳細 Study of TRP Channels by Automated Patch Clamp Systems
    Year: 2010 First author: Sunesen et al., 2010
  • 詳細 QPatch: the missing link between HTS and ion channel drug discovery.
    Year: 2009 First author: Mathes

Reports

  • 詳細 TRPM8 cold sensitive ion channels
    Year: 2012 First author: Jensen
  • 詳細 HEK293-TRPV1 on QPatch
    Year: 2011 First author: Jacobsen et al., 2011

P2X

Posters

  • 詳細 Pharmacological characterization of voltage- and ligand-gated ion channels
    Year: 2006 First author: Olsen et al., 2006

Papers

  • 詳細 Modulation of P2X3 and P2X2/3 Receptors by Monoclonal Antibodies
    Year: 2016 First author: Shcherbatko et al., 2016
  • 詳細 QPatch: the missing link between HTS and ion channel drug discovery.
    Year: 2009 First author: Mathes

Reports

  • 詳細 Validation of ligand-gated ion channels in multi-hole mode on QPatch
    Year: 2012 First author: Jacobsen et al., 2012
  • 詳細 CHO TREx-P2X3 on QPatch
    Year: 2008 First author: Schrøder et al., 2008

NMDA, AMPA and KA

Papers

  • 詳細 A novel substituted aminoquinoline selectively targets voltage-sensitive sodium channel isoforms and NMDA receptor subtypes and alleviates chronic inflammatory and neuropathic pain
    Year: 2016 First author: Tabakoff et al., 2016
  • 詳細 Positive allosteric modulators of α7 nicotinic acetylcholine receptors affect neither the function of other ligand- and voltage-gated ion channels and acetylcholinesterase, nor β-amyloid content
    Year: 2016 First author: Ariasa et al., 2016

ASIC1-3

Posters

  • 詳細 Application of QPatch 16 for drug screening of ligand-gated ion channels
    Year: 2005 First author: Andersen et al., 2005

Reports

  • 詳細 Ligand-gated ion channels on QPatch
    Year: 2012 First author: Jacobsen et al., 2012
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