Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ito, Takaya, Sakai, Atsushi, Maruyama, Motoyo, Miyagawa, Yoshitaka, Okada, Takashi, Fukayama, Haruhisa, Suzuki, Hidenori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
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
_version_ 1783511351078944768
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
work_keys_str_mv AT itotakaya dorsalrootgangliahomeoboxdownregulationinprimarysensoryneuronscontributestoneuropathicpaininrats
AT sakaiatsushi dorsalrootgangliahomeoboxdownregulationinprimarysensoryneuronscontributestoneuropathicpaininrats
AT maruyamamotoyo dorsalrootgangliahomeoboxdownregulationinprimarysensoryneuronscontributestoneuropathicpaininrats
AT miyagawayoshitaka dorsalrootgangliahomeoboxdownregulationinprimarysensoryneuronscontributestoneuropathicpaininrats
AT okadatakashi dorsalrootgangliahomeoboxdownregulationinprimarysensoryneuronscontributestoneuropathicpaininrats
AT fukayamaharuhisa dorsalrootgangliahomeoboxdownregulationinprimarysensoryneuronscontributestoneuropathicpaininrats
AT suzukihidenori dorsalrootgangliahomeoboxdownregulationinprimarysensoryneuronscontributestoneuropathicpaininrats