title: Optimal delineation of single C-tactile and C-nociceptive afferents in humans by latency slowing.
abstract: C-mechanoreceptors in humans comprise a population of unmyelinated afferents exhibiting a wide range of mechanical sensitivities. C-mechanoreceptors are putatively divided into those signaling gentle touch (C-tactile afferents, CTs) and nociception (C-mechanosensitive nociceptors, CMs), giving rise to positive and negative affect, respectively. We sought to distinguish, compare, and contrast the properties of a population of human C-mechanoreceptors to see how fundamental the divisions between these putative subpopulations are. We used microneurography to record from individual afferents in humans and applied electrical and mechanical stimulation to their receptive fields. We show that C-mechanoreceptors can be distinguished unequivocally into two putative populations, comprising CTs and CMs, by electrically evoked spike latency changes (slowing). After both natural mechanical stimulation and repetitive electrical stimulation there was markedly less latency slowing in CTs compared with CMs. Electrical receptive field stimulation, which bypasses the receptor end organ, was most effective in classifying C-mechanoreceptors, as responses to mechanical receptive field stimulation overlapped somewhat, which may lead to misclassification. Furthermore, we report a subclass of low-threshold CM responding to gentle mechanical stimulation and a potential subclass of CT afferent displaying burst firing. We show that substantial differences exist in the mechanisms governing axonal conduction between CTs and CMs. We provide clear electrophysiological "signatures" (extent of latency slowing) that can be used in unequivocally identifying populations of C-mechanoreceptors in single-unit and multiunit microneurography studies and in translational animal research into affective touch. Additionally, these differential mechanisms may be pharmacologically targetable for separate modulation of positive and negative affective touch information.NEW & NOTEWORTHYHuman skin encodes a plethora of touch interactions, and affective tactile information is primarily signaled by slowly conducting C-mechanoreceptive afferents. We show that electrical stimulation of low-threshold C-tactile afferents produces markedly different patterns of activity compared with high-threshold C-mechanoreceptive nociceptors, although the populations overlap in their responses to mechanical stimulation. This fundamental distinction demonstrates a divergence in affective touch signaling from the first stage of sensory processing, having implications for the processing of interpersonal touch.
authors.affiliation: Department of Physiology, University of Gothenburg, Gothenburg, Sweden; roger.holmes.watkins@gu.se.|School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom.
authors.forename: Roger H
authors.identifier: 0000-0001-5425-6579
authors.initials: RH
authors.lastname: Watkins
authors.affiliation: Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Wessberg
authors.affiliation: Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Backlund Wasling
authors.affiliation: University Division of Anaesthesia, Cambridge University Hospitals, NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: James P
authors.initials: JP
authors.lastname: Dunham
authors.affiliation: Department of Physiology, University of Gothenburg, Gothenburg, Sweden.|Center for Social and Affective Neuroscience, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden; and.
authors.forename: Håkan
authors.initials: H
authors.lastname: Olausson
authors.affiliation: Department of Physiology, University of Gothenburg, Gothenburg, Sweden.|Department of Physiological Sciences, University of Florida, Gainesville, Florida.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Johnson
authors.affiliation: Department of Physiology, University of Gothenburg, Gothenburg, Sweden.|Laboratoire de Neurosciences Intégratives et Adaptatives (UMR 7260), Aix-Marseille Université-CNRS, Marseille, France.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Ackerley
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000328:Adult; D000704:Analysis of Variance; D004558:Electric Stimulation; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology*; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D010812:Physical Stimulation; D011601:Psychophysics; D011930:Reaction Time / Q000502:physiology*; D012867:Skin / Q000294:innervation*; D014110:Touch / Q000502:physiology*; D055815:Young Adult
keywords: C fiber; human; low-threshold mechanoreceptor; microneurography; nociceptor