Spinal excitatory dynorphinergic interneurons contribute to burn injury-induced nociception mediated by phosphorylated histone 3 at serine 10 in rodents
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The phosphorylation of serine 10 in histone 3 (p-S10H3) has recently been demonstrated to participate in spinal nociceptive processing. However, superficial dorsal horn (SDH) neurons involved in p-S10H3-mediated nociception have not been fully characterized. In the present work, we combined immunohistochemistry, in situ hybridization with the retrograde labeling of projection neurons to reveal the subset of dorsal horn neurons presenting an elevated level of p-S10H3 in response to noxious heat (60 °C), causing burn injury. Projection neurons only represented a small percentage (5%) of p-S10H3-positive cells, while the greater part of them belonged to excitatory SDH interneurons. The combined immunolabeling of p-S10H3 with markers of already established interneuronal classes of the SDH revealed that the largest subset of neurons with burn injury-induced p-S10H3 expression was dynorphin immunopositive in mice. Furthermore, the majority of p-S10H3-expressing dynorphinergic neurons proved to be excitatory, as they lacked Pax-2 and showed Lmx1b-immunopositivity. Thus, we showed that neurochemically heterogeneous SDH neurons exhibit the upregulation of p-S10H3 shortly after noxious heat-induced burn injury and consequential tissue damage, and that a dedicated subset of excitatory dynorphinergic neurons is likely a key player in the development of central sensitization via the p-S10H3 mediated pathway.
Date Issued
2021-03-01
Date Acceptance
2021-02-21
Citation
International Journal of Molecular Sciences, 2021, 22 (5), pp.1-28
ISSN
1422-0067
Publisher
MDPI AG
Start Page
1
End Page
28
Journal / Book Title
International Journal of Molecular Sciences
Volume
22
Issue
5
Copyright Statement
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.mdpi.com/1422-0067/22/5/2297
Subjects
Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Biochemistry & Molecular Biology
Chemistry, Multidisciplinary
Chemistry
histone
epigenetic modification
superficial dorsal horn neuron
burn injury
neuropeptides
nociception
burn injury
epigenetic modification
histone
neuropeptides
nociception
superficial dorsal horn neuron
Animals
Burns
Epigenesis, Genetic
Female
Histones
Immunohistochemistry
In Situ Hybridization
LIM-Homeodomain Proteins
Male
Mice
Mice, Transgenic
Nociception
PAX2 Transcription Factor
Pain
Phosphorylation
Posterior Horn Cells
Rats
Rats, Wistar
Serine
Spinal Cord
Transcription Factors
Chemical Physics
0399 Other Chemical Sciences
0604 Genetics
0699 Other Biological Sciences
Publication Status
Published
Article Number
2297
Date Publish Online
2021-02-25