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Inhibition of spinal ferroptosis-like cell death alleviates hyperalgesia and spontaneous pain in a mouse model of bone cancer pain

Bone cancer pain (BCP) impairs patients’ quality of life. However, the underlying mechanisms are still unclear. This study investigated the role of spinal interneuron death using a pharmacological inhibitor of ferroptosis in a mouse model of BCP. Lewis lung carcinoma cells were inoculated into the f...

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Autores principales: Ding, Zhuofeng, Liang, Xiaoshen, Wang, Jian, Song, Zongbin, Guo, Qulian, Schäfer, Michael K.E., Huang, Changsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141498/
https://www.ncbi.nlm.nih.gov/pubmed/37084690
http://dx.doi.org/10.1016/j.redox.2023.102700
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author Ding, Zhuofeng
Liang, Xiaoshen
Wang, Jian
Song, Zongbin
Guo, Qulian
Schäfer, Michael K.E.
Huang, Changsheng
author_facet Ding, Zhuofeng
Liang, Xiaoshen
Wang, Jian
Song, Zongbin
Guo, Qulian
Schäfer, Michael K.E.
Huang, Changsheng
author_sort Ding, Zhuofeng
collection PubMed
description Bone cancer pain (BCP) impairs patients’ quality of life. However, the underlying mechanisms are still unclear. This study investigated the role of spinal interneuron death using a pharmacological inhibitor of ferroptosis in a mouse model of BCP. Lewis lung carcinoma cells were inoculated into the femur, resulting in hyperalgesia and spontaneous pain. Biochemical analysis revealed that spinal levels of reactive oxygen species and malondialdehyde were increased, while those of superoxide dismutase were decreased. Histological analysis showed the loss of spinal GAD65+ interneurons and provided ultrastructural evidence of mitochondrial shrinkage. Pharmacologic inhibition of ferroptosis using ferrostatin-1 (FER-1, 10 mg/kg, intraperitoneal for 20 consecutive days) attenuated ferroptosis-associated iron accumulation and lipid peroxidation and alleviated BCP. Furthermore, FER-1 inhibited the pain-associated activation of ERK1/2 and COX-2 expression and prevented the loss of GABAergic interneurons. Moreover, FER-1 improved analgesia by the COX-2 inhibitor Parecoxib. Taken together, this study shows that pharmacological inhibition of ferroptosis-like cell death of spinal interneurons alleviates BCP in mice. The results suggest that ferroptosis is a potential therapeutic target in patients suffering on BCP and possibly other types of pain.
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spelling pubmed-101414982023-04-29 Inhibition of spinal ferroptosis-like cell death alleviates hyperalgesia and spontaneous pain in a mouse model of bone cancer pain Ding, Zhuofeng Liang, Xiaoshen Wang, Jian Song, Zongbin Guo, Qulian Schäfer, Michael K.E. Huang, Changsheng Redox Biol Research Paper Bone cancer pain (BCP) impairs patients’ quality of life. However, the underlying mechanisms are still unclear. This study investigated the role of spinal interneuron death using a pharmacological inhibitor of ferroptosis in a mouse model of BCP. Lewis lung carcinoma cells were inoculated into the femur, resulting in hyperalgesia and spontaneous pain. Biochemical analysis revealed that spinal levels of reactive oxygen species and malondialdehyde were increased, while those of superoxide dismutase were decreased. Histological analysis showed the loss of spinal GAD65+ interneurons and provided ultrastructural evidence of mitochondrial shrinkage. Pharmacologic inhibition of ferroptosis using ferrostatin-1 (FER-1, 10 mg/kg, intraperitoneal for 20 consecutive days) attenuated ferroptosis-associated iron accumulation and lipid peroxidation and alleviated BCP. Furthermore, FER-1 inhibited the pain-associated activation of ERK1/2 and COX-2 expression and prevented the loss of GABAergic interneurons. Moreover, FER-1 improved analgesia by the COX-2 inhibitor Parecoxib. Taken together, this study shows that pharmacological inhibition of ferroptosis-like cell death of spinal interneurons alleviates BCP in mice. The results suggest that ferroptosis is a potential therapeutic target in patients suffering on BCP and possibly other types of pain. Elsevier 2023-04-12 /pmc/articles/PMC10141498/ /pubmed/37084690 http://dx.doi.org/10.1016/j.redox.2023.102700 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Ding, Zhuofeng
Liang, Xiaoshen
Wang, Jian
Song, Zongbin
Guo, Qulian
Schäfer, Michael K.E.
Huang, Changsheng
Inhibition of spinal ferroptosis-like cell death alleviates hyperalgesia and spontaneous pain in a mouse model of bone cancer pain
title Inhibition of spinal ferroptosis-like cell death alleviates hyperalgesia and spontaneous pain in a mouse model of bone cancer pain
title_full Inhibition of spinal ferroptosis-like cell death alleviates hyperalgesia and spontaneous pain in a mouse model of bone cancer pain
title_fullStr Inhibition of spinal ferroptosis-like cell death alleviates hyperalgesia and spontaneous pain in a mouse model of bone cancer pain
title_full_unstemmed Inhibition of spinal ferroptosis-like cell death alleviates hyperalgesia and spontaneous pain in a mouse model of bone cancer pain
title_short Inhibition of spinal ferroptosis-like cell death alleviates hyperalgesia and spontaneous pain in a mouse model of bone cancer pain
title_sort inhibition of spinal ferroptosis-like cell death alleviates hyperalgesia and spontaneous pain in a mouse model of bone cancer pain
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141498/
https://www.ncbi.nlm.nih.gov/pubmed/37084690
http://dx.doi.org/10.1016/j.redox.2023.102700
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