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TRPM3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is an adverse effect observed in up to 80% of patients of cancer on treatment with cytostatic drugs including paclitaxel and oxaliplatin. Chemotherapy-induced peripheral neuropathic pain can be so severe that it limits dose and choice of chemo...

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Autores principales: Aloi, Vincenzo Davide, Pinto, Sílvia João Poseiro Coutinho, Van Bree, Rita, Luyten, Katrien, Voets, Thomas, Vriens, Joris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10436359/
https://www.ncbi.nlm.nih.gov/pubmed/37079852
http://dx.doi.org/10.1097/j.pain.0000000000002906
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author Aloi, Vincenzo Davide
Pinto, Sílvia João Poseiro Coutinho
Van Bree, Rita
Luyten, Katrien
Voets, Thomas
Vriens, Joris
author_facet Aloi, Vincenzo Davide
Pinto, Sílvia João Poseiro Coutinho
Van Bree, Rita
Luyten, Katrien
Voets, Thomas
Vriens, Joris
author_sort Aloi, Vincenzo Davide
collection PubMed
description Chemotherapy-induced peripheral neuropathic pain (CIPNP) is an adverse effect observed in up to 80% of patients of cancer on treatment with cytostatic drugs including paclitaxel and oxaliplatin. Chemotherapy-induced peripheral neuropathic pain can be so severe that it limits dose and choice of chemotherapy and has significant negative consequences on the quality of life of survivors. Current treatment options for CIPNP are limited and unsatisfactory. TRPM3 is a calcium-permeable ion channel functionally expressed in peripheral sensory neurons involved in the detection of thermal stimuli. Here, we focus on the possible involvement of TRPM3 in acute oxaliplatin-induced mechanical allodynia and cold hypersensitivity. In vitro calcium microfluorimetry and whole-cell patch-clamp experiments showed that TRPM3 is functionally upregulated in both heterologous and homologous expression systems after acute (24 hours) oxaliplatin treatment, whereas the direct application of oxaliplatin was without effect. In vivo behavioral studies using an acute oxaliplatin model for CIPNP showed the development of cold and mechano hypersensitivity in control mice, which was lacking in TRPM3 deficient mice. In addition, the levels of protein ERK, a marker for neuronal activity, were significantly reduced in dorsal root ganglion neurons derived from TRPM3 deficient mice compared with control after oxaliplatin administration. Moreover, intraperitoneal injection of a TRPM3 antagonist, isosakuranetin, effectively reduced the oxaliplatin-induced pain behavior in response to cold and mechanical stimulation in mice with an acute form of oxaliplatin-induced peripheral neuropathy. In summary, TRPM3 represents a potential new target for the treatment of neuropathic pain in patients undergoing chemotherapy.
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spelling pubmed-104363592023-08-19 TRPM3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain Aloi, Vincenzo Davide Pinto, Sílvia João Poseiro Coutinho Van Bree, Rita Luyten, Katrien Voets, Thomas Vriens, Joris Pain Research Paper Chemotherapy-induced peripheral neuropathic pain (CIPNP) is an adverse effect observed in up to 80% of patients of cancer on treatment with cytostatic drugs including paclitaxel and oxaliplatin. Chemotherapy-induced peripheral neuropathic pain can be so severe that it limits dose and choice of chemotherapy and has significant negative consequences on the quality of life of survivors. Current treatment options for CIPNP are limited and unsatisfactory. TRPM3 is a calcium-permeable ion channel functionally expressed in peripheral sensory neurons involved in the detection of thermal stimuli. Here, we focus on the possible involvement of TRPM3 in acute oxaliplatin-induced mechanical allodynia and cold hypersensitivity. In vitro calcium microfluorimetry and whole-cell patch-clamp experiments showed that TRPM3 is functionally upregulated in both heterologous and homologous expression systems after acute (24 hours) oxaliplatin treatment, whereas the direct application of oxaliplatin was without effect. In vivo behavioral studies using an acute oxaliplatin model for CIPNP showed the development of cold and mechano hypersensitivity in control mice, which was lacking in TRPM3 deficient mice. In addition, the levels of protein ERK, a marker for neuronal activity, were significantly reduced in dorsal root ganglion neurons derived from TRPM3 deficient mice compared with control after oxaliplatin administration. Moreover, intraperitoneal injection of a TRPM3 antagonist, isosakuranetin, effectively reduced the oxaliplatin-induced pain behavior in response to cold and mechanical stimulation in mice with an acute form of oxaliplatin-induced peripheral neuropathy. In summary, TRPM3 represents a potential new target for the treatment of neuropathic pain in patients undergoing chemotherapy. Wolters Kluwer 2023-09 2023-04-19 /pmc/articles/PMC10436359/ /pubmed/37079852 http://dx.doi.org/10.1097/j.pain.0000000000002906 Text en Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Research Paper
Aloi, Vincenzo Davide
Pinto, Sílvia João Poseiro Coutinho
Van Bree, Rita
Luyten, Katrien
Voets, Thomas
Vriens, Joris
TRPM3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain
title TRPM3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain
title_full TRPM3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain
title_fullStr TRPM3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain
title_full_unstemmed TRPM3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain
title_short TRPM3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain
title_sort trpm3 as a novel target to alleviate acute oxaliplatin-induced peripheral neuropathic pain
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10436359/
https://www.ncbi.nlm.nih.gov/pubmed/37079852
http://dx.doi.org/10.1097/j.pain.0000000000002906
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