Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli

View ORCID ProfileMateusz W. Kucharczyk, Kim I. Chisholm, Franziska Denk, Anthony H. Dickenson, Kirsty Bannister, Stephen B. McMahon
doi: https://doi.org/10.1101/498980
Mateusz W. Kucharczyk
1Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, WC1E 6BT London, UK
2Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK
3Central Modulation of Pain Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mateusz W. Kucharczyk
  • For correspondence: mateusz.kucharczyk@kcl.ac.uk matwku@gmail.com
Kim I. Chisholm
2Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Franziska Denk
2Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anthony H. Dickenson
1Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, WC1E 6BT London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kirsty Bannister
3Central Modulation of Pain Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen B. McMahon
2Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Skeletal metastases are frequently accompanied by chronic pain that is mechanoceptive in nature and not easily managed by available therapies. The peripheral sensory profile of primary afferents responsible for transmitting the pain-related messages from cancerous bone to central sites is investigated here. We imaged thousands of primary sensory dorsal root ganglion neurons in vivo in healthy (sham-operated) and cancer-induced bone pain (CIBP) rats in order to analyse and compare their function. Utilising Markov Cluster Analysis we identified distinct clusters of primary afferent responses to limb compression and position. In CIBP rats, three times as many sensory afferents responded to knee compression in the leg ipsilateral to the tumour compared to sham-operated rats. We present evidence that the observed increase in sensory afferent response was not due to increased individual afferent activity but rather represents activation of ‘silent’ nociceptors, whose origin we propose is largely from outside of the bone.

Footnotes

  • We have updated the analysis of neuronal responses applying Markov Cluster Analysis. This largely unsupervised method of clustering large longitudinal data was adopted here, for the first time, in order to cluster neuronal responses to defined stimuli. It revealed several primary afferent types responding differently to mechanical forces applied to the peripheral receptive field. Therefore, the emphasis of the manuscript in now on the impact of bone cancer on the peripheral encoding of mechanical pressure stimuli, rather than the mechanisms underlying 'unsilencing' of silent nociceptors. We believe, that a more thorough analysis of the involvement of Piezo2 mechanosensor needs to be performed (i.e. using murine KO for the channel, rather than presented in the earlier version of the manuscript block with the spider toxin) and it can be a direction for future studies. Advillin data has been removed and will constitute a separate article focusing on the role of Advillin negative afferents. The ATF3 studies will be included in the Advillin paper. Manuscript was modified accordingly given the changes made.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted September 10, 2019.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli
Mateusz W. Kucharczyk, Kim I. Chisholm, Franziska Denk, Anthony H. Dickenson, Kirsty Bannister, Stephen B. McMahon
bioRxiv 498980; doi: https://doi.org/10.1101/498980
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli
Mateusz W. Kucharczyk, Kim I. Chisholm, Franziska Denk, Anthony H. Dickenson, Kirsty Bannister, Stephen B. McMahon
bioRxiv 498980; doi: https://doi.org/10.1101/498980

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (4087)
  • Biochemistry (8762)
  • Bioengineering (6479)
  • Bioinformatics (23341)
  • Biophysics (11750)
  • Cancer Biology (9149)
  • Cell Biology (13248)
  • Clinical Trials (138)
  • Developmental Biology (7417)
  • Ecology (11369)
  • Epidemiology (2066)
  • Evolutionary Biology (15087)
  • Genetics (10399)
  • Genomics (14009)
  • Immunology (9121)
  • Microbiology (22040)
  • Molecular Biology (8779)
  • Neuroscience (47368)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2482)
  • Physiology (3704)
  • Plant Biology (8050)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2208)
  • Systems Biology (6016)
  • Zoology (1249)