Breakthroughs in the Development of Non-Opioid Pain Analgesics: How Sodium Ion Channels Inhibitors Could Replace Opioids
Significant Advances in Pain Research Based on Sodium Ion Channels (Nav) Located in the Peripheral Nervous System (PNS)
For many years, researchers have targeted Nav1.7 and Nav1.8 sodium channels due to their localization in the Peripheral Nervous System (PNS). Nav1.8 channels reside almost exclusively in neurons of the Dorsal Root Ganglion (DRG), while Nav1.7 channels reside primarily in the PNS but also to some degree in the central nervous system (CNS). Blockade of either Nav1.7 or Nav1.8 sodium channels may attenuate the pain signal in the PNS prior to the pain signal’s entrance into the CNS.
Figure: Schematic of the mechanism by which Nav1.8 participates in the pain pathway. (Recreated in BioRender.com application from Ye, P. et al., Acta Biochim. Biophys. Sin., 2016)
Na channel inhibitors in the PNS are good candidates to replace highly addictive opioids that act in the CNS and PNS. The development of Nav1.8 or Nav1.7 inhibitors, that don’t cross the blood brain barrier, should also have a low probability of causing addiction and would be a welcome substitute for highly addictive opioids.
Access Eurofins DiscoverX® ion channel product solutions for Nav (Nav1.7, Nav1.8, or all Nav products).
The US Food and Drug Administration (FDA) Approval of Novel Non-Opioid Treatment for Moderate to Severe Acute Pain
Suzetriginne (brand name Journavx
Inhibition of PNS Ion Channel Pain Receptors
There is evidence from clinical studies that blockade of the Nav1.8 channel does not completely block transmission of the pain signal in the PNS (Jones J. et al. 2023). Inhibition of PNS ion channel pain receptors, in addition to the Nav1.8 channel, could potentially attenuate the pain signal in the PNS prior to the signal entering the CNS. This suggests a combination drug inhibiting Nav1.8 and peripheral ion channels could be beneficial. Peripheral ion channels include transient receptor potential (TRP) channels, acid sensing channels (ASIC), or other channels such as potassium channels (KCNQ). Learn more (see Bean, Bruce, AnaBios Webinar 2025). Activation of potassium channels, like KCNQ channels located in the PNS, by a combination drug may also attenuate the pain signal by reducing neuronal excitability.
Access Eurofins DiscoverX® product solutions for peripheral ion channels TRP, ASIC, and KCNQ (Kv7 potassium channels).
Use of Eurofins DiscoverX’s Cell Lines for the Recent Development of Novel Nav Inhibitors by Latigo Therapeutics
Latigo Biotherapeutics used Eurofins DiscoverX’s Nav1.8 stable cell lines (CYL3025 and CYL3050) to develop the novel Nav1.8 inhibitor, LTGO-33 (Gilchrist J., et al. 2024). Learn more (2025 webinar recap blog). Latigo also received fast track designation for the Latigo compound (LTG-001) from the FDA for the development of a potential best-in-class Nav1.8 inhibitor.
SiteOne Therapeutics has made recent advances targeting Nav1.7 and Nav1.8 channels to treat acute and chronic pain. Their primary drug candidate, STC-004, inhibits Nav1.8 channels and shows favorable results in Phase 1 clinical trials. Recently (2025), they were acquired by Eli Lilly in a deal worth up to $1 billion.
Conclusions
Significant advances in pain management have been made with the discovery of potent inhibitors of the Nav1.8 channel that successfully attenuate pain in clinical studies. Targeting Nav1.8 or Nav1.7 channels in the PNS is a very appealing alternative to managing pain with highly addictive opioids. Further progress may be made in pain management by modulation of other pain receptors in addition to the sodium channels in the PNS.