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Novel mechanisms of bone cancer pain revealed with in vivo GCaMP6s imaging

View ORCID ProfileMateusz W. Kucharczyk, Kim I. Chisholm, Douglas M. Lopes, Diane Derrien, Franziska Denk, Kirsty Bannister, Anthony H. Dickenson, Stephen B. McMahon
doi: https://doi.org/10.1101/498980
Mateusz W. Kucharczyk
Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, WC1E 6BT London, UK Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK Central Modulation of Pain Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK
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  • ORCID record for Mateusz W. Kucharczyk
  • For correspondence: mateusz.kucharczyk@kcl.ac.uk matwku@gmail.com
Kim I. Chisholm
Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK
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Douglas M. Lopes
Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK
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Diane Derrien
Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, WC1E 6BT London, UK
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Franziska Denk
Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK
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Kirsty Bannister
Central Modulation of Pain Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK
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Anthony H. Dickenson
Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, WC1E 6BT London, UK
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Stephen B. McMahon
Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King’s College London, London SE1 1UL, UK
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Abstract

Cancer pain remains a major area of unmet medical need, with few studies existing in proportion to that need. One common form, affecting 400,000 people each year in the US alone, is associated with skeletal metastases. These pains are typically mechanoceptive in nature and poorly managed by available analgesics. Here, we employed in vivo imaging using GCaMP6s to assess the properties of the nerve fibres that convey bone cancer pains. We find that a subclass of nociceptors, those that are normally mechanically insensitive, are recruited and activated in a rodent model of bone cancer, and this dramatically increases sensory input from the diseased tissue to the central nervous system. The recruitment of these so-called silent afferents was found to be Piezo2-dependent. The unique properties of these silent afferents offer several novel opportunities for targeting metastatic bone pain.

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Posted December 17, 2018.
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Novel mechanisms of bone cancer pain revealed with in vivo GCaMP6s imaging
Mateusz W. Kucharczyk, Kim I. Chisholm, Douglas M. Lopes, Diane Derrien, Franziska Denk, Kirsty Bannister, Anthony H. Dickenson, Stephen B. McMahon
bioRxiv 498980; doi: https://doi.org/10.1101/498980
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Novel mechanisms of bone cancer pain revealed with in vivo GCaMP6s imaging
Mateusz W. Kucharczyk, Kim I. Chisholm, Douglas M. Lopes, Diane Derrien, Franziska Denk, Kirsty Bannister, Anthony H. Dickenson, Stephen B. McMahon
bioRxiv 498980; doi: https://doi.org/10.1101/498980

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