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Mechanosensory encoding dysfunction emerges from cancer-chemotherapy interaction
Persistent sensory, motor and cognitive disabilities comprise chemotherapy-induced neural disorders (CIND) that limit quality of life with little therapeutic relief for cancer survivors. Our recent preclinical study provides new insight into a condition impacting the severity of chronic CIND. We fin...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9729348/ https://www.ncbi.nlm.nih.gov/pubmed/36504708 http://dx.doi.org/10.3389/fmolb.2022.1017427 |
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author | Housley, Stephen N. Nardelli, Paul Rotterman, Travis M. Reed, J’Ana Cope, Timothy C. |
author_facet | Housley, Stephen N. Nardelli, Paul Rotterman, Travis M. Reed, J’Ana Cope, Timothy C. |
author_sort | Housley, Stephen N. |
collection | PubMed |
description | Persistent sensory, motor and cognitive disabilities comprise chemotherapy-induced neural disorders (CIND) that limit quality of life with little therapeutic relief for cancer survivors. Our recent preclinical study provides new insight into a condition impacting the severity of chronic CIND. We find that sensorimotor disability observed following cancer treatment exceeds that attributable to chemotherapy alone. A possible explanation for intensified disability emerged from evidence that codependent effects of cancer and chemotherapy amplify defective firing in primary sensory neurons supplying one type of low threshold mechanosensory receptor (LTMR). Here we test whether cancer’s modification of chemotherapy-induced sensory defects generalizes across eight LTMR submodalities that collectively generate the signals of origin for proprioceptive and tactile perception and guidance of body movement. Preclinical study enabled controlled comparison of the independent contributions of chemotherapy and cancer to their clinically relevant combined effects. We compared data sampled from rats that were otherwise healthy or bearing colon cancer and treated, or not, with human-scaled, standard-of-care chemotherapy with oxaliplatin. Action potential firing patterns encoding naturalistic mechanical perturbations of skeletal muscle and skin were measured electrophysiologically in vivo from multiple types of LTMR neurons. All expressed aberrant encoding of dynamic and/or static features of mechanical stimuli in healthy rats treated with chemotherapy, and surprisingly also by some LTMRs in cancer-bearing rats that were not treated. By comparison, chemotherapy and cancer in combination worsened encoding aberrations, especially in slowly adapting LTMRs supplying both muscle and glabrous skin. Probabilistic modeling best predicted observed encoding defects when incorporating interaction effects of cancer and chemotherapy. We conclude that for multiple mechanosensory submodalities, the severity of encoding defects is modulated by a codependence of chemotherapy side effects and cancer’s systemic processes. We propose that the severity of CIND might be reduced by therapeutically targeting the mechanisms, yet to be determined, by which cancer magnifies chemotherapy’s neural side effects as an alternative to reducing chemotherapy and its life-saving benefits. |
format | Online Article Text |
id | pubmed-9729348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97293482022-12-09 Mechanosensory encoding dysfunction emerges from cancer-chemotherapy interaction Housley, Stephen N. Nardelli, Paul Rotterman, Travis M. Reed, J’Ana Cope, Timothy C. Front Mol Biosci Molecular Biosciences Persistent sensory, motor and cognitive disabilities comprise chemotherapy-induced neural disorders (CIND) that limit quality of life with little therapeutic relief for cancer survivors. Our recent preclinical study provides new insight into a condition impacting the severity of chronic CIND. We find that sensorimotor disability observed following cancer treatment exceeds that attributable to chemotherapy alone. A possible explanation for intensified disability emerged from evidence that codependent effects of cancer and chemotherapy amplify defective firing in primary sensory neurons supplying one type of low threshold mechanosensory receptor (LTMR). Here we test whether cancer’s modification of chemotherapy-induced sensory defects generalizes across eight LTMR submodalities that collectively generate the signals of origin for proprioceptive and tactile perception and guidance of body movement. Preclinical study enabled controlled comparison of the independent contributions of chemotherapy and cancer to their clinically relevant combined effects. We compared data sampled from rats that were otherwise healthy or bearing colon cancer and treated, or not, with human-scaled, standard-of-care chemotherapy with oxaliplatin. Action potential firing patterns encoding naturalistic mechanical perturbations of skeletal muscle and skin were measured electrophysiologically in vivo from multiple types of LTMR neurons. All expressed aberrant encoding of dynamic and/or static features of mechanical stimuli in healthy rats treated with chemotherapy, and surprisingly also by some LTMRs in cancer-bearing rats that were not treated. By comparison, chemotherapy and cancer in combination worsened encoding aberrations, especially in slowly adapting LTMRs supplying both muscle and glabrous skin. Probabilistic modeling best predicted observed encoding defects when incorporating interaction effects of cancer and chemotherapy. We conclude that for multiple mechanosensory submodalities, the severity of encoding defects is modulated by a codependence of chemotherapy side effects and cancer’s systemic processes. We propose that the severity of CIND might be reduced by therapeutically targeting the mechanisms, yet to be determined, by which cancer magnifies chemotherapy’s neural side effects as an alternative to reducing chemotherapy and its life-saving benefits. Frontiers Media S.A. 2022-11-24 /pmc/articles/PMC9729348/ /pubmed/36504708 http://dx.doi.org/10.3389/fmolb.2022.1017427 Text en Copyright © 2022 Housley, Nardelli, Rotterman, Reed and Cope. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Housley, Stephen N. Nardelli, Paul Rotterman, Travis M. Reed, J’Ana Cope, Timothy C. Mechanosensory encoding dysfunction emerges from cancer-chemotherapy interaction |
title | Mechanosensory encoding dysfunction emerges from cancer-chemotherapy interaction |
title_full | Mechanosensory encoding dysfunction emerges from cancer-chemotherapy interaction |
title_fullStr | Mechanosensory encoding dysfunction emerges from cancer-chemotherapy interaction |
title_full_unstemmed | Mechanosensory encoding dysfunction emerges from cancer-chemotherapy interaction |
title_short | Mechanosensory encoding dysfunction emerges from cancer-chemotherapy interaction |
title_sort | mechanosensory encoding dysfunction emerges from cancer-chemotherapy interaction |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9729348/ https://www.ncbi.nlm.nih.gov/pubmed/36504708 http://dx.doi.org/10.3389/fmolb.2022.1017427 |
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