In this week's episode of the Spine & Nerve podcast Drs. Nicolas Karvelas and Brian Joves take a look back at basic physiology to try to look into the future. An area of research that has really piqued the interest of Dr. Karvelas in recent years has been the discussion/possibility of selective voltage gated sodium channel (NaV) modulators. NaV are transmembrane proteins that are an integral part of the initiation and propagation of action potentials in neurons and other electrically excitable cells. We have seen that small changes in NaV function are biologically relevant because there are several human diseases that are the result of mutations in these channels. This has led to research into selective NaV modulators as a potential target as we continue to search for treatment options with significant analgesic potential and decreased risk of side effects / adverse effects. The medical / research community continues to work to optimize medication options to treat painful disease processes. From an analgesic medication perspective, although there are a variety of different medications available including: topical medications, acetaminophen, non-steroidal anti-inflammatory drugs, gabapentin, pregabalin, serotonin norepinephrine reuptake inhibitors, tricyclic anti-depressant medications, non-selective sodium channel blockers, NMDA receptor modulations (Memantine, Ketamine), alpha-2 agonists, glial cell modulators (Low Dose Naltrexone), Buprenorphine, full mu opioids. These Medications are not without their limitations for multiple reasons including but not limited to side effects, risks, and contraindications depending on patient’s age and/or comorbidities. To the best of our knowledge there are 10 different NaV subtypes; and specifically NaV 1.3, 1.7, 1.8, 1.9 have been demonstrated to play a critical role in pain signaling. NaV 1.8 is a sensory neuron specific channel with preferential expression in the dorsal root ganglion and trigeminal ganglion neurons, and it is highly expressed on nociceptors. Similar to the other NaV subtypes that have been identified to play essential roles in pain, mutations in NaV 1.8 have been demonstrated to lead to significant alterations in the nervous system / pain pathways; specifically gain of function NaV 1.8 mutations clinically manifest as painful small fiber peripheral polyneuropathy. NaV 1.8 modulation is being aggressively researched with the goal of positive impact on painful diseases. VX-150 is a oral pro-drug that is a highly selective inhibitor of NaV1.8, and a recent study by Dr. Hijma and colleagues was published evaluating the analgesic potential and safety of VX-150. Listen as the doctors discuss this exciting and important area of research. The discussion includes a detailed review of the fore-mentioned recent research article. This podcast is for information and educational purposes only, it is not meant to be medical or career advice. If anything discussed may pertain to you, please seek council with your healthcare provider. The views expressed are those of the individuals expressing them, they may not represent the views of Spine & Nerve. References: 1. Hijma HJ, Siebenga PS, de Kam ML, Groeneveld GJ. A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Pharmacodynamic Effects of VX-150, a Highly Selective NaV1.8 Inhibitor, in Healthy Male Adults. Pain Med. 2021 Aug 6;22(8):1814-1826.