Pain
Pain is usually defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, so pain is an important mechanism for preventing injury. The sense of pain occurs as the brain responds to input from the periphery. Electrical and chemical changes that appear because of an injury, disease or damage to the body are conducted centrally by means of a whole array of ion channels, some initiate the stimulus, some conduct electrically, and some transmit chemically across synapses.
There are two basic types of pain: neuropathic (nerve injury) pain and nociceptive (tissue) pain.
Neuropathic pain is caused by a primary lesion or dysfunction in the nervous system, and it lasts long after healing of the damaged tissues and can turn into chronic pain. Nociceptive pain occurs when nociceptors are substances stimulated by damaged or inflamed tissue. The pain is usually time-limited and serves a protective purpose.
There are many examples of ion channels involved in pain, and they play different roles. Voltage-gated Na+ channels are important for conduction along afferent nerve fibres, voltage-gated Ca2+ channels are important for releasing neurotransmitters in the synaptic cleft and transient receptor potential ion channels (TRP), acid-sensing ion channels (ASIC), glutamate receptors (KA, NMDA and AMPA ligand-gated ion channels) are involved in the primary response at the free terminals placed under the skin.
Selection of ion channels involved in pain sensation and transmission:
Key Pain Ion Channels
Nav1.1, 1.6, 1.7 & 1.8 (1.3 after injury)
Cav1.2, 2.2
TRP
P2X
NMDA, AMPA and KA
ASIC1-3
Nav1.1, 1.3, 1,4, 1.6, 1.7 & 1.8
Posters
- View Adaptive voltage protocols increase precision of voltage-gated ion channel measurements on highthroughput automated patch clamp platforms Year: 2019
- View Biophysical and pharmacological profiling of multiple voltage-gated sodium channel subtypes on QPatch II Year: 2019
- View Biophysical and pharmacological characterization of multiple Nav subtypes on Qube Year: 2016
- View CHO-hNav1.7 assay on Qube pharmacology, biophysical characterization and the effect of internal fluoride Year: 2017
- View Sophion analyzer as a tool for biophysical and pharmacological characterization of eight Nav subtypes evaluated in parallel on Qube Year: 2016
- View HT Automation for patch clamp based primary screen for Nav1.1 using Qube 384 Year: 2018
- View Biophysical and pharmacological profiling of multiple Nav subtypes on QPatch HT Year: 2016
- View “Clip Detecting” with series resistance compensation using an automated patch clamp system Year: 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
- View Multi-parameter ion channel screening: mechanism-of-action data directly from HTS Year: 2019
- View Adaptive voltage control ensures the precise half inactivation application of voltage-gated channels on automated patch clamp system Year: 2019
Papers
- View Selective Nav1.7 Antagonists with Long Residence Time Show Improved Efficacy against Inflammatory and Neuropathic Pain Year: 2018
- View Efficient Enzymatic Ligation of Inhibitor Cystine Knot Spider Venom Peptides: Using Sortase A To Form Double-Knottins That Probe Voltage-Gated Sodium Channel NaV1.7 Year: 2018
- View Direct evidence for high affinity blockade of NaV1.6 channel subtype by huwentoxin-IV spider peptide, using multiscale functional approaches Year: 2018
- View The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/− mice Year: 2017
- View Manipulation of a spider peptide toxin alters its affinity for lipid bilayers and potency and selectivity for voltage-gated sodium channel subtype Year: 2020
- View High-Throughput Screening of Nav1.7 Modulators Using a Giga-Seal Automated Patch Clamp Instrument Year: 2016
- View The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and Excitatory Activities on Human NaV1.6 Year: 2018
- View Identification and Electrophysiological Evaluation of 2-Methylbenzamide Derivatives as Nav1.1 Modulators Year: 2015
- View 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
- View Engineering Highly Potent and Selective Microproteins Against Nav1.7 Sodium Channel for Treatment of Pain Year: 2016
- View Rational engineering defines a molecular switch that is essential for activity of spider-venom peptides against the analgesics target Nav1.7 Year: 2015
- View Using automated patch clamp electrophysiology platforms in pain-related ion channel research: insights from industry and academia Year: 2017
- View From identification to functional characterization of cyriotoxin-1a, an antinociceptive toxin from the spider Cyriopagopus schioedtei. Year: 2019
- View Development of a high-throughput fluorescent no-wash sodium influx assay Year: 2019
- View Structure- and Ligand-Based Discovery of Chromane Arylsulfonamide Nav1.7 Inhibitors for the Treatment of Chronic Pain Year: 2019
- View Mapping the Molecular Surface of the Analgesic Nav1.7-Selective Peptide Pn3a Reveals Residues Essential for Membrane and Channel Interactions Year: 2020
- View Fluorescence labeling of a Nav1.7-targeted peptide for near-infrared nerve visualization Year: 2020
- View Characterization of Synthetic Tf2 as a Nav1.3 Selective Pharmacological Probe Year: 2020
- View Recombinant production, bioconjugation and membrane binding studies of Pn3a, a selective Nav1.7 inhibitor Year: 2020
- View Pharmacological activity and NMR solution structure of the leech peptide HSTX-I Year: 2020
- View Screening Assay Protocols Targeting the Nav1.7 Channel Using Qube High‐Throughput Automated Patch‐Clamp System Year: 2020
- View Enzymatic Ligation of a Pore Blocker Toxin and a Gating Modifier Toxin: Creating Double-Knotted Peptides with Improved Sodium Channel Nav1.7 Inhibition Year: 2019
- View Neurotoxic peptides from the venom of the giant Australian stinging tree Year: 2020
- View The Snake with the Scorpion’s Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake Year: 2016
- View Nav1.7-P610T mutation in 2 siblings with persistent ocular pain after corneal axon transection: impaired slow-inactivation and hyperexcitable trigeminal neurons Year: 2023
Reports
Cav1.2
Posters
Papers
- View A new classifier-based strategy for in-silico ion-channel cardiac drug safety assessment Year: 2015
- View Screening system for drug-induced arrhythmogenic risk combining a patch clamp and heart simulator Year: 2015
- View MICE Models: Superior to the HERG Model in Predicting Torsade de Pointes Year: 2013
Reports
Cav2.2
Papers
- View Discovery and optimization of a novel series of pyrazolyltetrahydropyran N-type calcium channel (Cav 2.2) blockers for the treatment of pain Year: 2018
TRP
Posters
Papers
- View In vitro characterization of the thermoneutral transient receptor potential vanilloid-1 (TRPV1) inhibitor GRTE16523 Year: 2020
- View The development of automated patch clamp assays for canonical transient receptor potential channels TRPC3, 6, and 7 Year: 2014
- View Study of TRP Channels by Automated Patch Clamp Systems Year: 2010
- View QPatch: the missing link between HTS and ion channel drug discovery. Year: 2009
Reports
P2X
Posters
Papers
Reports
NMDA, AMPA and KA
Posters
- View Development and validation of NMDA ligand-gated ion channel assays using the Qube 384 automated electrophysiology platform Year: 2019
Papers
- View A novel substituted aminoquinoline selectively targets voltage-sensitive sodium channel isoforms and NMDA receptor subtypes and alleviates chronic inflammatory and neuropathic pain Year: 2016
- View 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
ASIC1-3
Posters
- View Application of QPatch 16 for drug screening of ligand-gated ion channels Year: 2005