Old Friends With New Faces: Are Sodium Channel Blockers the Future of Adjunct Pain Medication Management?

•Specific subtypes of voltage-gated sodium channels (Nav1.1-1.9) have been linked to inflammatory and nociceptive pain.•Pharmacokinetic studies reveal misconceived drug interactions with oxcarbazepine.•Carbamazepine and oxcarbazepine may be currently underutilized for certain pain syndromes.•There is a call for additional research for carboxamide subclass of sodium channel blockers in pain. Providers are being asked to decrease the emphasis and overutilization of long-term opioid therapy, but many are left without proper guidance on appropriate utilization of nonopioid therapies. Furthermore, therapeutic options are quite limited and many providers lack confidence in distinguishing available alternatives. When first-line therapy has failed in a patient, there is an apparent lack of knowledge on how to proceed with choosing subsequent therapy. To choose among alternative agents, an understanding of pharmacology, pharmacokinetics, and efficacy in targeting various pain conditions is necessary. This article focuses on the use of the carboxamide class of sodium channel blockers (carbamazepine, oxcarbazepine, eslicarbazepine) for adjunct pain medication management including research updates in pharmacology, pharmacokinetics, and current evidence for pain along with promising areas of research. It is an evidence update for clinical use of sodium channel blockers, clarifies misconceptions regarding their use, and highlights emerging research for improved pain targets that justifies additional study. We performed a complete review of the literature using the search terms, “oxcarbazepine,” “carbamazepine,” and “eslicarbazepine” in conjunction with “pharmacokinetics,” “adverse effects,” “pharmacology,” “voltage-gated sodium channel subtype,” “neuropathic pain,” “inflammatory pain,” “metabolism,” “epoxide metabolite formation,” “drug interactions,” “CYP450 interactions,” “pain phenotype,” and “chronic pain management.” Databases searched included PubMed and Google Scholar. Package inserts were used for drug structure illustration, adverse reactions, and bioavailability. Pharmacology and pharmacokinetic data were taken from randomized controlled trials evaluating this area as well as in vitro published results. For validity, only peer-reviewed literature was included. Evidence for sodium channel blockers in chronic pain management was limited. This review focuses on highlighting the data available for the use of sodium channel blockers for certain pain syndromes as we