Axonal sensitivity and block dynamics

The role of differential nerve block in the development of analgesia after erector spinae plane block has been questioned. While highly myelinated nerves are more sensitive to local anesthetics than unmyelinated ones in vitro, factors influencing drug diffusion, particularly pKa, are more relevant in the clinical setting. Bupivacaine (the drug most used for an 'analgesic' effect) has a relatively high pKa (8.1), and only 15% of it is present in the lipid permeant, unionized form at pH 7.4 so it will penetrate unmyelinated C fibers relatively easily, but the myelin sheaths around other fiber types are a significant barrier to drug diffusion. The greater sensitivity of myelinated axons to local anesthetic action will only be apparent if the drug can reach their membranes in significant concentrations. In the very dynamic situation pertaining to a local anesthetic injection (no matter the site), diffusion factors mean that the concentration of the drug around the axons is likely to be very low and may result in an effect on unmyelinated fibers only.