Spinal signaling of C-fiber mediated pleasant touch in humans

  1. Andrew G Marshall  Is a corresponding author
  2. Manohar L Sharma
  3. Kate Marley
  4. Hakan Olausson
  5. Francis P McGlone
  1. University of Liverpool, United Kingdom
  2. Walton Centre NHS Foundation Trust, United Kingdom
  3. University Hospital Aintree, United Kingdom
  4. Linköping University, Sweden
  5. Liverpool John Moores University, United Kingdom


C-tactile afferents form a distinct channel that encodes pleasant tactile stimulation. Prevailing views indicate they project, as with other unmyelinated afferents, in lamina I-spinothalamic pathways. However, we found that spinothalamic ablation in humans, whilst profoundly impairing pain, temperature and itch, had no effect on pleasant touch perception. Only discriminative touch deficits were seen. These findings preclude privileged C-tactile-lamina I-spinothalamic projections and imply integrated hedonic and discriminative spinal processing from the body.

Data availability

All data generated or analysed during this study are either included in the manuscript and supporting files or Open Science Framework - accession code g8vyk

The following data sets were generated

Article and author information

Author details

  1. Andrew G Marshall

    Institute of Aging and Chronic Disease, University of Liverpool, Liverpool, United Kingdom
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8273-7089
  2. Manohar L Sharma

    Department of Pain Medicine, Walton Centre NHS Foundation Trust, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Kate Marley

    Specialist Palliative Care Team, University Hospital Aintree, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Hakan Olausson

    Center for Social and Affective Neuroscience, Linköping University, Linköping, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Francis P McGlone

    School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.


Pain Relief Foundation

  • Andrew G Marshall

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Human subjects: Ethical approval was obtained through the Health Research Authority National Research Ethics Service (Preston NRES committee, study reference 14/NW/1247). The study was conducted in accordance with the Declaration of Helsinki. Written informed consent was taken from all study participants.

Reviewing Editor

  1. Peggy Mason, University of Chicago, United States

Publication history

  1. Received: September 5, 2019
  2. Accepted: December 23, 2019
  3. Accepted Manuscript published: December 24, 2019 (version 1)
  4. Version of Record published: January 16, 2020 (version 2)


© 2019, Marshall et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


  • 2,492
    Page views
  • 375
  • 30

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Andrew G Marshall
  2. Manohar L Sharma
  3. Kate Marley
  4. Hakan Olausson
  5. Francis P McGlone
Spinal signaling of C-fiber mediated pleasant touch in humans
eLife 8:e51642.

Further reading

    1. Neuroscience
    Jan Boelts et al.
    Research Advance Updated

    Inferring parameters of computational models that capture experimental data are a central task in cognitive neuroscience. Bayesian statistical inference methods usually require the ability to evaluate the likelihood of the model—however, for many models of interest in cognitive neuroscience, the associated likelihoods cannot be computed efficiently. Simulation-based inference (SBI) offers a solution to this problem by only requiring access to simulations produced by the model. Previously, Fengler et al. introduced likelihood approximation networks (LANs, Fengler et al., 2021) which make it possible to apply SBI to models of decision-making, but require billions of simulations for training. Here, we provide a new SBI method that is substantially more simulation efficient. Our approach, mixed neural likelihood estimation (MNLE), trains neural density estimators on model simulations to emulate the simulator, and is designed to capture both the continuous (e.g., reaction times) and discrete (choices) data of decision-making models. The likelihoods of the emulator can then be used to perform Bayesian parameter inference on experimental data using standard approximate inference methods like Markov Chain Monte Carlo sampling. We demonstrate MNLE on two variants of the drift-diffusion model and show that it is substantially more efficient than LANs: MNLE achieves similar likelihood accuracy with six orders of magnitude fewer training simulations, and is significantly more accurate than LANs when both are trained with the same budget. Our approach enables researchers to perform SBI on custom-tailored models of decision-making, leading to fast iteration of model design for scientific discovery.

    1. Computational and Systems Biology
    2. Neuroscience
    Vasileios Dimakopoulos et al.
    Research Article

    The maintenance of items in working memory (WM) relies on a widespread network of cortical areas and hippocampus where synchronization between electrophysiological recordings reflects functional coupling. We investigated the direction of information flow between auditory cortex and hippocampus while participants heard and then mentally replayed strings of letters in WM by activating their phonological loop. We recorded local field potentials from the hippocampus, reconstructed beamforming sources of scalp EEG, and – additionally in four participants – recorded from subdural cortical electrodes. When analyzing Granger causality, the information flow was from auditory cortex to hippocampus with a peak in the [4 8] Hz range while participants heard the letters. This flow was subsequently reversed during maintenance while participants maintained the letters in memory. The functional interaction between hippocampus and the cortex and the reversal of information flow provide a physiological basis for the encoding of memory items and their active replay during maintenance.