Advances in the Pharmacology of Local Anesthetics: Molecular Actions, Delivery Systems, and Safety Considerations

Local anesthetics remain a cornerstone of modern clinical practice, yet the pharmacology underpinning their use continues to evolve. At the molecular level, new work is deepening our understanding of how these agents interact with voltage-gated sodium channels (NaV), modulate membrane dynamics, and engage intracellular signaling pathways. In parallel, advances in NaV subtype pharmacology are informing the design of next-generation analgesics with improved selectivity and reduced off-target effects — an area of growing relevance to both anesthesiology and pain medicine.On the translational side, significant effort has been directed toward extending the duration and precision of anesthetic effects. These efforts span the characterization of approved extended-release formulations, novel lipid- and polymer-based delivery platforms, and nanotechnology-enabled systems — all aimed at improving tissue targeting, reducing systemic exposure, and enhancing patient outcomes.Safety remains a defining challenge in this field. Local anesthetic systemic toxicity (LAST) — encompassing cardiotoxicity, neurotoxicity, and the molecular pathways that drive them — continues to attract both mechanistic investigation and clinical attention. Advances in the pharmacological basis of lipid emulsion rescue therapy and other interventional strategies are broadening the toolkit available to clinicians.This Research Topic brings together contributions spanning basic pharmacology, formulation science, and translational research. By assembling mechanistic, preclinical, and clinically oriented work in one collection, it aims to offer an integrated and up-to-date resource for investigators and practitioners working in anesthesia, pain management, and drug development.Areas of interest include, but are not limited to:Molecular and cellular mechanisms of local anesthetic action, including ion channel modulation, membrane interactions, and intracellular signaling pathwaysAdvances in voltage-gated sodium channel (NaV) pharmacology, with a focus on subtype selectivity and NaV-targeted analgesic developmentExtended- and sustained-release delivery systems for local anesthetics, spanning approved formulations and novel translational platformsLocal anesthetic systemic toxicity (LAST): mechanistic insights into cardiotoxicity and neurotoxicity, and advances in clinical management including lipid emulsion therapy Topic editors: Kotaro Hori, Takashi Mori, Michael Lenaeus Source: https://www.frontiersin.org/research-topics/83546/advances-in-the-pharmacology-of-local-anesthetics-molecular-actions-delivery-systems-and-safety-considerations