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Involvement of Histone Lysine Crotonylation in the Regulation of Nerve-Injury-Induced Neuropathic Pain

Histone lysine crotonylation (KCR), a novel epigenetic modification, is important in regulating a broad spectrum of biological processes and various diseases. However, whether KCR is involved in neuropathic pain remains to be elucidated. We found KCR occurs in macrophages, sensory neurons, and satel...

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Autores principales: Zou, Yu, Bai, Xue-Hui, Kong, Ling-Chi, Xu, Fei-Fei, Ding, Ting-Yu, Zhang, Peng-Fei, Dong, Fu-Lu, Ling, Yue-Juan, Jiang, Bao-Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329947/
https://www.ncbi.nlm.nih.gov/pubmed/35911694
http://dx.doi.org/10.3389/fimmu.2022.885685
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author Zou, Yu
Bai, Xue-Hui
Kong, Ling-Chi
Xu, Fei-Fei
Ding, Ting-Yu
Zhang, Peng-Fei
Dong, Fu-Lu
Ling, Yue-Juan
Jiang, Bao-Chun
author_facet Zou, Yu
Bai, Xue-Hui
Kong, Ling-Chi
Xu, Fei-Fei
Ding, Ting-Yu
Zhang, Peng-Fei
Dong, Fu-Lu
Ling, Yue-Juan
Jiang, Bao-Chun
author_sort Zou, Yu
collection PubMed
description Histone lysine crotonylation (KCR), a novel epigenetic modification, is important in regulating a broad spectrum of biological processes and various diseases. However, whether KCR is involved in neuropathic pain remains to be elucidated. We found KCR occurs in macrophages, sensory neurons, and satellite glial cells of trigeminal ganglia (TG), neurons, astrocytes, and microglia of the medulla oblongata. KCR in TG was detected mainly in small and medium sensory neurons, to a lesser extent in large neurons. Peripheral nerve injury elevated KCR levels in macrophages in the trigeminal and dorsal root ganglia and microglia in the medulla oblongata but reduced KCR levels in sensory neurons. Inhibition of histone crotonyltransferases (p300) by intra-TG or intrathecal administration of C646 significantly alleviated partial infraorbital nerve transection (pIONT)- or spinal nerve ligation (SNL)-induced mechanical allodynia and thermal hyperalgesia. Intra-TG or intrathecal administration of Crotonyl coenzyme A trilithium salt to upregulate KCR dose-dependently induced mechanical allodynia and thermal hyperalgesia in mice. Mechanismly, inhibition of p300 alleviated pIONT-induced macrophage activation and reduced the expression of pain-related inflammatory cytokines Tnfα, Il1β and chemokines Ccl2 and Cxcl10. Correspondingly, exogenous crotonyl-CoA induced macrophage activation and the expression of Tnfα, Il1β, Il6, Ccl2 and Ccl7 in TG, which C646 can repress. These findings suggest that histone crotonylation might be functionally involved in neuropathic pain and neuroinflammation regulation.
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spelling pubmed-93299472022-07-29 Involvement of Histone Lysine Crotonylation in the Regulation of Nerve-Injury-Induced Neuropathic Pain Zou, Yu Bai, Xue-Hui Kong, Ling-Chi Xu, Fei-Fei Ding, Ting-Yu Zhang, Peng-Fei Dong, Fu-Lu Ling, Yue-Juan Jiang, Bao-Chun Front Immunol Immunology Histone lysine crotonylation (KCR), a novel epigenetic modification, is important in regulating a broad spectrum of biological processes and various diseases. However, whether KCR is involved in neuropathic pain remains to be elucidated. We found KCR occurs in macrophages, sensory neurons, and satellite glial cells of trigeminal ganglia (TG), neurons, astrocytes, and microglia of the medulla oblongata. KCR in TG was detected mainly in small and medium sensory neurons, to a lesser extent in large neurons. Peripheral nerve injury elevated KCR levels in macrophages in the trigeminal and dorsal root ganglia and microglia in the medulla oblongata but reduced KCR levels in sensory neurons. Inhibition of histone crotonyltransferases (p300) by intra-TG or intrathecal administration of C646 significantly alleviated partial infraorbital nerve transection (pIONT)- or spinal nerve ligation (SNL)-induced mechanical allodynia and thermal hyperalgesia. Intra-TG or intrathecal administration of Crotonyl coenzyme A trilithium salt to upregulate KCR dose-dependently induced mechanical allodynia and thermal hyperalgesia in mice. Mechanismly, inhibition of p300 alleviated pIONT-induced macrophage activation and reduced the expression of pain-related inflammatory cytokines Tnfα, Il1β and chemokines Ccl2 and Cxcl10. Correspondingly, exogenous crotonyl-CoA induced macrophage activation and the expression of Tnfα, Il1β, Il6, Ccl2 and Ccl7 in TG, which C646 can repress. These findings suggest that histone crotonylation might be functionally involved in neuropathic pain and neuroinflammation regulation. Frontiers Media S.A. 2022-07-14 /pmc/articles/PMC9329947/ /pubmed/35911694 http://dx.doi.org/10.3389/fimmu.2022.885685 Text en Copyright © 2022 Zou, Bai, Kong, Xu, Ding, Zhang, Dong, Ling and Jiang 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 Immunology
Zou, Yu
Bai, Xue-Hui
Kong, Ling-Chi
Xu, Fei-Fei
Ding, Ting-Yu
Zhang, Peng-Fei
Dong, Fu-Lu
Ling, Yue-Juan
Jiang, Bao-Chun
Involvement of Histone Lysine Crotonylation in the Regulation of Nerve-Injury-Induced Neuropathic Pain
title Involvement of Histone Lysine Crotonylation in the Regulation of Nerve-Injury-Induced Neuropathic Pain
title_full Involvement of Histone Lysine Crotonylation in the Regulation of Nerve-Injury-Induced Neuropathic Pain
title_fullStr Involvement of Histone Lysine Crotonylation in the Regulation of Nerve-Injury-Induced Neuropathic Pain
title_full_unstemmed Involvement of Histone Lysine Crotonylation in the Regulation of Nerve-Injury-Induced Neuropathic Pain
title_short Involvement of Histone Lysine Crotonylation in the Regulation of Nerve-Injury-Induced Neuropathic Pain
title_sort involvement of histone lysine crotonylation in the regulation of nerve-injury-induced neuropathic pain
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329947/
https://www.ncbi.nlm.nih.gov/pubmed/35911694
http://dx.doi.org/10.3389/fimmu.2022.885685
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