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Dorsal Root Ganglia Homeobox downregulation in primary sensory neurons contributes to neuropathic pain in rats
Transcriptional changes in primary sensory neurons are involved in initiation and maintenance of neuropathic pain. However, the transcription factors in primary sensory neurons responsible for neuropathic pain are not fully understood. Dorsal Root Ganglia Homeobox (DRGX) is a paired-like homeodomain...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099666/ https://www.ncbi.nlm.nih.gov/pubmed/32000573 http://dx.doi.org/10.1177/1744806920904462 |
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author | Ito, Takaya Sakai, Atsushi Maruyama, Motoyo Miyagawa, Yoshitaka Okada, Takashi Fukayama, Haruhisa Suzuki, Hidenori |
author_facet | Ito, Takaya Sakai, Atsushi Maruyama, Motoyo Miyagawa, Yoshitaka Okada, Takashi Fukayama, Haruhisa Suzuki, Hidenori |
author_sort | Ito, Takaya |
collection | PubMed |
description | Transcriptional changes in primary sensory neurons are involved in initiation and maintenance of neuropathic pain. However, the transcription factors in primary sensory neurons responsible for neuropathic pain are not fully understood. Dorsal Root Ganglia Homeobox (DRGX) is a paired-like homeodomain transcription factor necessary for the development of nociceptive primary sensory neurons during the early postnatal period. However, roles for DRGX after development are largely unknown. Here, we report that DRGX downregulation in primary sensory neurons as a result of post-developmental nerve injury contributes to neuropathic pain in rats. DRGX expression was decreased in nuclei of small and medium primary sensory neurons after spinal nerve ligation. DRGX downregulation by transduction of a short hairpin RNA with an adeno-associated viral vector induced mechanical allodynia and thermal hyperalgesia. In contrast, DRGX overexpression in primary sensory neurons suppressed neuropathic pain. DRGX regulated matrix metalloproteinase-9 (MMP-9) and prostaglandin E receptor 2 mRNA expression in the DRG. MMP-9 inhibitor attenuated DRGX downregulation-induced pain. These results suggest that DRGX downregulation after development contributes to neuropathic pain through transcriptional modulation of pain-related genes in primary sensory neurons. |
format | Online Article Text |
id | pubmed-7099666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-70996662020-04-03 Dorsal Root Ganglia Homeobox downregulation in primary sensory neurons contributes to neuropathic pain in rats Ito, Takaya Sakai, Atsushi Maruyama, Motoyo Miyagawa, Yoshitaka Okada, Takashi Fukayama, Haruhisa Suzuki, Hidenori Mol Pain Research Article Transcriptional changes in primary sensory neurons are involved in initiation and maintenance of neuropathic pain. However, the transcription factors in primary sensory neurons responsible for neuropathic pain are not fully understood. Dorsal Root Ganglia Homeobox (DRGX) is a paired-like homeodomain transcription factor necessary for the development of nociceptive primary sensory neurons during the early postnatal period. However, roles for DRGX after development are largely unknown. Here, we report that DRGX downregulation in primary sensory neurons as a result of post-developmental nerve injury contributes to neuropathic pain in rats. DRGX expression was decreased in nuclei of small and medium primary sensory neurons after spinal nerve ligation. DRGX downregulation by transduction of a short hairpin RNA with an adeno-associated viral vector induced mechanical allodynia and thermal hyperalgesia. In contrast, DRGX overexpression in primary sensory neurons suppressed neuropathic pain. DRGX regulated matrix metalloproteinase-9 (MMP-9) and prostaglandin E receptor 2 mRNA expression in the DRG. MMP-9 inhibitor attenuated DRGX downregulation-induced pain. These results suggest that DRGX downregulation after development contributes to neuropathic pain through transcriptional modulation of pain-related genes in primary sensory neurons. SAGE Publications 2020-01-31 /pmc/articles/PMC7099666/ /pubmed/32000573 http://dx.doi.org/10.1177/1744806920904462 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Research Article Ito, Takaya Sakai, Atsushi Maruyama, Motoyo Miyagawa, Yoshitaka Okada, Takashi Fukayama, Haruhisa Suzuki, Hidenori Dorsal Root Ganglia Homeobox downregulation in primary sensory neurons contributes to neuropathic pain in rats |
title | Dorsal Root Ganglia Homeobox downregulation in primary sensory neurons contributes to neuropathic pain in rats |
title_full | Dorsal Root Ganglia Homeobox downregulation in primary sensory neurons contributes to neuropathic pain in rats |
title_fullStr | Dorsal Root Ganglia Homeobox downregulation in primary sensory neurons contributes to neuropathic pain in rats |
title_full_unstemmed | Dorsal Root Ganglia Homeobox downregulation in primary sensory neurons contributes to neuropathic pain in rats |
title_short | Dorsal Root Ganglia Homeobox downregulation in primary sensory neurons contributes to neuropathic pain in rats |
title_sort | dorsal root ganglia homeobox downregulation in primary sensory neurons contributes to neuropathic pain in rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099666/ https://www.ncbi.nlm.nih.gov/pubmed/32000573 http://dx.doi.org/10.1177/1744806920904462 |
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