Anesthesiology 2001; 95:1441–54 © 2001 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Preferential Block of Small Myelinated Sensory and Motor Fibers by Lidocaine In Vivo Electrophysiology in the Rat Sciatic Nerve Alexander P. Gokin, Ph.D.,* Benjamin Philip,† Gary R. Strichartz, Ph.D.‡ Background: Controversy still surrounds the differential sus- ceptibility of nerve fibers to local anesthetics and its relation to selective functional deficits. In the current study we report features of conduction blockade in different classes of rat sciatic nerve fibers after injection of lidocaine by a percutaneous pro- cedure that closely resembles clinical applications. Methods: In 30 adult male Sprague-Dawley rats (weight, 300 – 400 g) during general anesthesia, impulses were recorded in different classes of sensory axons (large, A and  fibers; small, A myelinated fibers and unmyelinated C fibers) and motor axons (large, A fibers; small, A myelinated fibers) classified by conduction velocity. The sciatic nerve was stimulated dis- tally, and impulses were recorded from small filaments teased from L4 –L5 dorsal (sensory) and ventral (motor) roots sec- tioned acutely from the spinal cord. Lidocaine at concentration of 0.05–1% was injected percutaneously in 0.1-ml solutions at the sciatic notch. Both tonic (stimulated at 0.5 Hz) and use- dependent (stimulated at 40 Hz for A and A fibers and at 5 Hz for C fibers) impulse inhibitions by lidocaine were assayed. Results: Minimal effective (threshold) lidocaine concentra- tions (i.e., to block conduction in 10% of fibers) were, for sensory, 0.03% for A, 0.07% for A, and 0.09–0.1% for C fibers, and for motor, 0.03% for A and 0.05% for A fibers. The order of fiber susceptibility, ranked by concentrations that gave peak tonic fiber blockade of 50% (IC 50s ), was A > A  A > A > C. Faster-conducting C fibers (conduction velocity > 1 m/s) were more susceptible (IC 50  0.13%) than slower ones (conduction velocity < 1 m/s; IC 50  0.30%). At 1% lidocaine, all fibers were tonically blocked. Use-dependent effects accounted for only a modest potentiation of block (at a lidocaine concen- tration of 0.25%) in A and A fibers, and in C fibers phasic stimulation had even smaller effects and sometimes relieved tonic block. Conclusions: Susceptibility to lidocaine does not strictly fol- low the “size principle” that smaller (slower) axons are always blocked first. This order of fiber blockade is qualitatively con- sistent with previous reports of the order of functional deficits in the rat after percutaneous lidocaine, that is, motor  propri- oception > nociception, if we assume that motor deficits first arise from conduction failure in A fibers and that nociception relies on C fiber conduction. THE differential blockade of conduction by local anes- thetics in nerve fibers of different diameter was first described by Gasser and Erlanger. 1 They found that within the myelinated (A-group) fibers of the dog and frog, cocaine reduced the compound action potential components from slower-conducting (smaller-diameter) fibers more rapidly than those from faster-conducting (larger) fibers. This original observation has been reex- amined and generally confirmed by many studies on different peripheral nerves and spinal root fibers. In different animals and for different local anesthetics, small myelinated (e.g.,A) fibers have been found to be more susceptible to local anesthetic (LA) block than larger myelinated (A,A) fibers. 2–7 These findings led to for- mulation of the “size principle” of differential block, which states that susceptibility to LA depends inversely on fiber diameter. However, this size principle is not universally true. For instance, it was found that the smaller, preganglionic, myelinated B fibers in rabbit va- gus nerve were less susceptible than the larger A fibers to local anesthetic block. Nor was this principle appli- cable to the whole continuum of myelinated and unmy- elinated fibers. 8 –11 Earlier reports clearly noted that the LA susceptibility of many C fibers (e.g., in dorsal roots or saphenous nerve of the cat assayed in vivo) was com- parable to or even less than that of the faster A fi- bers. 5,6 . Recently Huang et al. 12 , using a perfusion cell to achieve equilibrium block by lidocaine of rat sciatic nerve in vivo, showed that C-fiber nociceptors were three or four times less susceptible to block than A nociceptors or A mechanoreceptors. The characteristics of differential impulse block may vary among different peripheral nerves, among different local anesthetics, and even among different animal spe- cies (e.g., frog, rat, cat, and human) (see review by Raymond and Gissen 13 ). Differential block cannot be predicted a priori, certainly not on the basis of the classic size principle. Nevertheless, physiologic observa- tions and clinical experience provide evidence that dif- ferential block of impulses in nerve fibers exists, depend- ing on anatomic features, critical duration of drug exposure, or some other, function-related property. This belief is the basis for exploring principles and mecha- nisms of LA action to understand and, eventually, to produce functionally selective nerve blocks. This article is featured in “This Month in Anesthesiology.” Please see this issue of ANESTHESIOLOGY, page 5A.  * Instructor in Anesthesia, † Research Assistant, ‡ Professor of Anesthesia (Pharmacology). Received from the Department of Anesthesiology, Preoperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. Submitted for publication August 16, 2000. Accepted for publi- cation July 23, 2001. Supported by United States Public Health Service grant No. GM35647 from the National Institutes of Health, Bethesda, Maryland (to Dr. Strichartz). Presented in part at the 28th annual meeting of the Society for Neuroscience, Los Angeles, California, November 7–12, 1998. Address reprint requests to Dr. Strichartz: Pain Research Center, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts, 02115. Address electronic mail to: gstrichz@zeus.bwh.harvard.edu. Individual article reprints may be purchased from the Journal Web site, www.anesthesiology.org. Anesthesiology, V 95, No 6, Dec 2001 1441 Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/95/6/1441/333655/0000542-200112000-00025.pdf by guest on 08 November 2021