The Science of Local Anesthesia: Basic Research, Clinical Application, and Future Directions

Local anesthetics have been used clinically for more than a century, but new insights into their mechanisms of action and their interaction with biological systems continue to surprise researchers and clinicians alike. Next to their classic action on voltage-gated sodium channels, local anesthetics interact with calcium, potassium, and hyperpolarization-gated ion channels, ligand-gated channels, and G protein–coupled receptors. They activate numerous downstream pathways in neurons, and affect the structure and function of many types of membranes. Local anesthetics must traverse several tissue barriers to reach their site of action on neuronal membranes. In particular, the perineurium is a major rate-limiting step. Allergy to local anesthetics is rare, while the variation in individual patient's response to local anesthetics is probably larger than previously assumed. Several adjuncts are available to prolong sensory block, but these typically also prolong motor block. The 2 main research avenues being followed to improve action of local anesthetics are to prolong duration of block, by slow-release formulations and on-demand release, and to develop compounds and combinations that elicit a nociception-selective blockade. Accepted for publication October 16, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Markus W. Hollmann, MD, PhD, Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Address e-mail to m.w.hollmann@amc.uva.nl. © 2017 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AU7J9E