{"id":20047,"date":"2026-10-08T09:09:05","date_gmt":"2026-10-08T09:09:05","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/?post_type=case-study&p=20047"},"modified":"2026-10-08T09:09:06","modified_gmt":"2026-10-08T09:09:06","slug":"advancing-pain-research-with-na%e1%b5%a51-7-and-na%e1%b5%a51-8-electrophysiology","status":"publish","type":"case-study","link":"https:\/\/www.sygnaturediscovery.com\/fr\/case-study\/advancing-pain-research-with-na%e1%b5%a51-7-and-na%e1%b5%a51-8-electrophysiology\/","title":{"rendered":"Advancing Pain Research with Na\u1d651.7 and Na\u1d651.8 Electrophysiology"},"content":{"rendered":"\n

Chronic pain remains one of the most significant unmet needs in drug discovery. While many current therapies can provide symptom relief, concerns around efficacy, tolerability, and dependence continue to drive the search for alternative approaches. Among the most widely studied targets are the voltage-gated sodium channels NaV<\/sub>1.7 and NaV<\/sub>1.8, which play distinct but complementary roles in peripheral pain signaling (Table 1).<\/p>\n\n\n

\n\t \n\t\n\t\t\t\t\t\t\n\t\t \t\t\n\t\t\t\t\t\t\t\n\t\t\t
\n
\n
\n \n \n \n \n \n <\/tbody>\n\n <\/table>\n <\/div>\n<\/div>\n\n\n
\n
\n \n
\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
\n
\n Table 1. NaV1.7\/1.8 activity in pain signaling\n <\/div>\n <\/th>\n <\/tr>\n <\/thead>\n \n
\n
\n
\n

Na\u1d651.7<\/strong><\/h2>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

\n
\n
\n

Na\u1d651.8<\/strong><\/span><\/h2>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

\n
\n
\n

Amplifies small depolarizations<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

\n
\n
\n

Generates large inward sodium current<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

\n
\n
\n

Helps the neuron reach action threshold<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

\n
\n
\n

Supports the generation of action potential<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n

\n
\n
\n

Initiates pain signaling<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n \n \n \n \n \n

\n
\n
\n

Supports action potential propagation<\/p>\n\n <\/div>\n <\/div>\n <\/td>\n <\/tr>\n <\/tbody>\n\n <\/table>\n <\/div>\n<\/div>\n\n\n

\n
\n \n \n \n \n \n <\/tbody>\n\n <\/table>\n <\/div>\n<\/div>\n\n<\/div>\n\t\t\n\t <\/section>\n\n\n\n
\"Diagram
Figure 1<\/strong>. Neuronal hypersensitivity mediated by Na\u1d651.7 and Na\u1d651.8 in chronic pain conditions<\/figcaption><\/figure>\n\n\n\n

Genetic and physiological studies have established NaV<\/sub>1.7 as a key regulator of pain perception. Loss-of-function mutations in the channel are associated with congenital insensitivity to pain, while gain-of-function mutations can lead to severe pain disorders. NaV<\/sub>1.8, by contrast, is expressed predominantly in nociceptive sensory neurons and contributes to the generation and propagation of action potentials associated with painful stimuli. Together, the two channels are widely investigated as targets for the development of non-opioid analgesics.<\/p>\n\n\n\n

\"Representative
Figure 2.<\/strong> Example of I-V activation current traces measured from Na\u1d651.8 cells (n=23); a series of pulses increasing in +10 mV steps from -110 mV to +60 mV are applied from a holding potential of -120 mV every 20 s.<\/figcaption><\/figure>\n\n\n\n

For drug developers pursuing these targets, one of the principal challenges is distinguishing meaningful pharmacology from broad sodium channel inhibition. Small differences in selectivity can have significant implications for efficacy, safety, and the overall progression of a discovery program. This places considerable importance on generating reliable functional data early in the drug discovery process.<\/p>\n\n\n\n

Why Sygnature Discovery?<\/strong><\/h2>\n\n\n\n

Understanding sodium channel pharmacology requires both reliable functional measurements and the ability to compare activity across closely related channel subtypes. Sygnature Discovery has developed a sodium channel electrophysiology platform spanning recombinant NaV<\/sub>1.1-1.8 assays together with human iPSC-derived sensory neuron models, enabling evaluation of both target engagement and subtype selectivity.<\/p>\n\n\n\n

\"Current
Figure 3.<\/strong> Electrophysiological profiling across recombinant Na\u1d65 channel subtypes enables comparison of channel behavior and supports assessment of subtype selectivity.<\/figcaption><\/figure>\n\n\n\n

Rather than relying on a single screening approach, researchers can combine automated electrophysiology, manual patch clamp studies and sensory neuron assays to investigate how compounds interact with pain-relevant sodium channels. This enables functional activity to be assessed in both controlled recombinant systems and more physiologically relevant cellular models. For organisations developing sodium channel-targeted pain therapeutics, understanding whether compounds demonstrate meaningful subtype selectivity is critical. Generating reliable functional data that differentiates activity across closely related sodium channel subtypes remains an important challenge during hit identification and lead optimization.<\/p>\n\n\n\n

Our Approach to the Challenge\u2026<\/strong><\/h2>\n\n\n\n

The program focused on generating electrophysiological data to characterise pain-relevant sodium channels, with particular emphasis on NaV<\/sub>1.8 pharmacology and comparative assessment with NaV<\/sub>1.7 activity. Automated patch clamp methods were used to measure sodium currents under defined voltage-clamp conditions and to evaluate the effects of pharmacological modulators on channel function.<\/p>\n\n\n\n

Particular emphasis was placed on NaV<\/sub>1.8, a target of growing interest for peripheral pain indications. Characterization studies examined channel activation and inactivation properties, assay stability, and pharmacological responses using reference compounds. Concentration-response experiments with the selective NaV<\/sub>1.8 inhibitor A803467 demonstrated reproducible inhibition across independent runs, providing an internal benchmark for assay performance (figure 4).<\/p>\n\n\n\n

\"Concentration-response
Figure 4.<\/strong> Concentration-response curve showing the concentration-dependent block in the presence of the specific NaV1.8 antagonist, A803467 over 3 different runs on the same day, and a table with the calculated IC50 for each run. <\/figcaption><\/figure>\n\n\n\n

The broader sodium channel platform also enabled comparison between closely related channel subtypes, helping to identify compounds with differentiated activity profiles and supporting selectivity assessment during lead optimization (figure 5).<\/p>\n\n\n\n

\"Diagram
Figure 5.<\/strong> Differential responses observed between NaV1.7 and NaV1.8 demonstrate the value of subtype profiling when evaluating sodium channel modulators.<\/figcaption><\/figure>\n\n\n\n

The work demonstrated that NaV<\/sub>1.8 activity can be measured reproducibly using standardised electrophysiology workflows, while the broader platform supports comparative assessment of additional sodium channel subtypes, including NaV<\/sub>1.7. Across the NaV<\/sub>1.8 assay, consistent current amplitudes, high proportions of successful recordings and reproducible responses to reference compounds indicated stable assay performance (figure 6 and 7).<\/p>\n\n\n\n

\"Bar
Figure 6.<\/strong> Sodium current amplitude (nA) measured across different days, consistently showing NaV1.8 currents above -1.5 nA.<\/figcaption><\/figure>\n\n\n\n
\"Bar
Figure 7.<\/strong> Number of positive cells (in %) measured across different days, consistently showing above 60% success rate.<\/figcaption><\/figure>\n\n\n\n

Importantly, the data highlighted the value of functional electrophysiology when studying sodium channels. While binding and indirect screening approaches can provide useful information, direct measurement of channel activity can provide additional insight into how compounds influence ion flow and neuronal excitability. This can be particularly relevant for programs seeking to differentiate molecules based on efficacy, state dependence or subtype selectivity.<\/p>\n\n\n\n

Our Impact on Pain-Relief Discovery Programs<\/strong><\/h2>\n\n\n\n

Access to functional data across both NaV<\/sub>1.7 and NaV<\/sub>1.8 enabled comparison of compound activity within a pain-relevant sodium channel panel. This provided additional context for evaluating pharmacological profiles and supported progression decisions during optimization activities.<\/p>\n\n\n\n

By integrating recombinant channel assays with human sensory neuron capabilities, programs could also begin to explore whether activity observed in reductionist systems translated into more biologically relevant models. This creates a framework for progressing from initial screening data towards a broader understanding of how compounds may behave in pain-related cellular systems.<\/p>\n\n\n\n

For organizations developing next-generation pain therapeutics, confidence in sodium channel data is essential. Reliable electrophysiology studies support compound prioritization, provide evidence for progression decisions and help focus resources on molecules with the most promising pharmacological profiles.<\/p>\n\n\n\n

As interest in NaV<\/sub>1.7\/1.8 continues to grow, access to robust functional assays and translationally relevant models provides a practical foundation for advancing non-opioid pain discovery programs and supporting key development decisions.<\/p>\n\n\n\n

Key Takeaways<\/strong><\/h2>\n\n\n\n
    \n
  • NaV<\/sub>1.7\/1.8 continues to be widely investigated as targets for non-opioid pain therapies.<\/li>\n\n\n\n
  • Understanding subtype-selective pharmacology is important for evaluating efficacy and safety risk.<\/li>\n\n\n\n
  • Functional electrophysiology provides direct measurement of sodium channel activity and pharmacology.<\/li>\n\n\n\n
  • Reproducible NaV<\/sub>1.8 data using reference inhibitors demonstrated consistent assay performance.<\/li>\n\n\n\n
  • Human sensory neuron models can provide additional biological context beyond recombinant systems.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":20053,"template":"","category":[706,681,707,746,692,753,778],"resource_tag":[1405],"class_list":["post-20047","case-study","type-case-study","status-publish","has-post-thumbnail","hentry","category-assay-development","category-bioscience","category-electrophysiology","category-ion-channels","category-lead-optimisation","category-neuroscience","category-sodium-channels","resource_tag-assays"],"acf":[],"yoast_head":"\nAdvancing Pain Research with Na\u1d651.7 and Na\u1d651.8 Electrophysiology<\/title>\n<meta name=\"description\" content=\"How NaV1.7 and NaV1.8 electrophysiology assays at Sygnature Discovery support confident decision making in non-opioid pain relief research.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.sygnaturediscovery.com\/fr\/case-study\/advancing-pain-research-with-na%e1%b5%a51-7-and-na%e1%b5%a51-8-electrophysiology\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Advancing Pain Research with Na\u1d651.7 and Na\u1d651.8 Electrophysiology\" \/>\n<meta property=\"og:description\" content=\"How NaV1.7 and NaV1.8 electrophysiology assays at Sygnature Discovery support confident decision making in non-opioid pain relief research.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.sygnaturediscovery.com\/fr\/case-study\/advancing-pain-research-with-na%e1%b5%a51-7-and-na%e1%b5%a51-8-electrophysiology\/\" \/>\n<meta property=\"og:site_name\" content=\"Sygnature\" \/>\n<meta property=\"article:modified_time\" content=\"2026-10-08T09:09:06+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/10\/Schematic-of-NaV1.7-1.8-in-chronic-pain.webp\" \/>\n\t<meta property=\"og:image:width\" content=\"655\" \/>\n\t<meta property=\"og:image:height\" content=\"456\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/webp\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Estimation du temps de lecture\" \/>\n\t<meta name=\"twitter:data1\" content=\"6 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/case-study\\\/advancing-pain-research-with-na%e1%b5%a51-7-and-na%e1%b5%a51-8-electrophysiology\\\/\",\"url\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/case-study\\\/advancing-pain-research-with-na%e1%b5%a51-7-and-na%e1%b5%a51-8-electrophysiology\\\/\",\"name\":\"Advancing Pain Research with Na\u1d651.7 and Na\u1d651.8 Electrophysiology\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/case-study\\\/advancing-pain-research-with-na%e1%b5%a51-7-and-na%e1%b5%a51-8-electrophysiology\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/case-study\\\/advancing-pain-research-with-na%e1%b5%a51-7-and-na%e1%b5%a51-8-electrophysiology\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/wp-content\\\/uploads\\\/2026\\\/10\\\/Schematic-of-NaV1.7-1.8-in-chronic-pain.webp\",\"datePublished\":\"2026-10-08T09:09:05+00:00\",\"dateModified\":\"2026-10-08T09:09:06+00:00\",\"description\":\"How NaV1.7 and NaV1.8 electrophysiology assays at Sygnature Discovery support confident decision making in non-opioid pain relief research.\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/case-study\\\/advancing-pain-research-with-na%e1%b5%a51-7-and-na%e1%b5%a51-8-electrophysiology\\\/#breadcrumb\"},\"inLanguage\":\"fr-CA\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/case-study\\\/advancing-pain-research-with-na%e1%b5%a51-7-and-na%e1%b5%a51-8-electrophysiology\\\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"fr-CA\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/case-study\\\/advancing-pain-research-with-na%e1%b5%a51-7-and-na%e1%b5%a51-8-electrophysiology\\\/#primaryimage\",\"url\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/wp-content\\\/uploads\\\/2026\\\/10\\\/Schematic-of-NaV1.7-1.8-in-chronic-pain.webp\",\"contentUrl\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/wp-content\\\/uploads\\\/2026\\\/10\\\/Schematic-of-NaV1.7-1.8-in-chronic-pain.webp\",\"width\":655,\"height\":456,\"caption\":\"Figure 1. 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