Conduction Properties Distinguish Unmyelinated Sympathetic Efferent Fibers and Unmyelinated Primary Afferent Fibers in the Monkey Matthias Ringkamp1*, Lisa M. Johanek1¤a, Jasenka Borzan2, Timothy V. Hartke1, Gang Wu1¤b, Esther M. Pogatzki-Zahn1¤c, James N. Campbell1, Beom Shim1¤d, Raf J. Schepers1¤e, Richard A. Meyer1,3 1 Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America, 2 Department of Anesthesiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America, 3 Applied Physics Laboratory, Johns Hopkins University, Baltimore, Maryland, United States of America Abstract Background: Different classes of unmyelinated nerve fibers appear to exhibit distinct conductive properties. We sought a criterion based on conduction properties for distinguishing sympathetic efferents and unmyelinated, primary afferents in peripheral nerves. Methodology/Principal Findings: In anesthetized monkey, centrifugal or centripetal recordings were made from single unmyelinated nerve fibers in the peroneal or sural nerve, and electrical stimuli were applied to either the sciatic nerve or the cutaneous nerve endings, respectively. In centrifugal recordings, electrical stimulation at the sympathetic chain and dorsal root was used to determine the fiber’s origin. In centrifugal recordings, sympathetic fibers exhibited absolute speeding of conduction to a single pair of electrical stimuli separated by 50 ms; the second action potential was conducted faster (0.61 + 0.16%) than the first unconditioned action potential. This was never observed in primary afferents. Following 2 Hz stimulation (3 min), activity-dependent slowing of conduction in the sympathetics (8.6 + 0.5%) was greater than in one afferent group (6.7 + 0.5%) but substantially less than in a second afferent group (29.4 + 1.9%). In centripetal recordings, most mechanically-insensitive fibers also exhibited absolute speeding to twin pulse stimulation. The subset that did not show this absolute speeding was responsive to chemical stimuli (histamine, capsaicin) and likely consists of mechanically- insensitive afferents. During repetitive twin pulse stimulation, mechanosensitive afferents developed speeding, and speeding in sympathetic fibers increased. Conclusions/Significance: The presence of absolute speeding provides a criterion by which sympathetic efferents can be differentiated from primary afferents. The differences in conduction properties between sympathetics and afferents likely reflect differential expression of voltage-sensitive ion channels. Citation: Ringkamp M, Johanek LM, Borzan J, Hartke TV, Wu G, et al. (2010) Conduction Properties Distinguish Unmyelinated Sympathetic Efferent Fibers and Unmyelinated Primary Afferent Fibers in the Monkey. PLoS ONE 5(2): e9076. doi:10.1371/journal.pone.0009076 Editor: Shawn Hochman, Emory University, United States of America Received October 22, 2009; Accepted January 11, 2010; Published February 5, 2010 Copyright: 2010 Ringkamp et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This research was supported by the National Institutes of Health (NS-14447 and NS-047399). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: platelet@jhmi.edu ¤a Current address: Medtronic, Incorporated, Minneapolis, Minnesota, United States of America ¤b Current address: Purdue Pharma, Cranberry, New Jersey, United States of America ¤c Current address: Department of Anesthesiology and Intensive Care, University Hospital Muenster, Muenster, Germany ¤d Current address: Amore Pacific, Seoul, Korea ¤e Current address: Medina, Dendermonde, Belgium Introduction Unmyelinated fibers in peripheral nerves can be broadly divided into two major groups, sympathetic efferent and primary afferent fibers. Primary afferent fibers have been divided further into different subgroups based on their responsiveness to mechanical, thermal and chemical stimuli. For example, some unmyelinated afferents exclusively respond to non-noxious mechanical [1] or warm stimuli [2]. Nociceptive unmyelinated afferents have been subdivided into those that are mechanosensitive or mechanoinsen- sitive. Some unmyelinated mechanoinsensitive nociceptive afferents are chemonociceptors and show lasting excitation following admi- nistration of capsaicin [3] or histamine [4,5]. The different functional classes of unmyelinated nerve fibers also differ in their conductive properties [6,7,8,9]. During repetitive electrical stimulation (2 Hz, 3 min), mechanosensitive and -insensitive nociceptive afferents exhibit marked increases (.20%) in conduction latency (‘slowing’ of conduction), whereas sympathetic efferents and ‘cold’ fibers slow less (,10%)[10,11]. These differences in activity-dependent conduction slowing are likely due to differences in expression of sodium channels in the axonal membrane [12,13]. PLoS ONE | www.plosone.org 1 February 2010 | Volume 5 | Issue 2 | e9076