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Article

Spinal Excitatory Dynorphinergic Interneurons Contribute to Burn Injury-Induced Nociception Mediated by Phosphorylated Histone 3 at Serine 10 in Rodents

1
MTA-DE-NAP B-Pain Control Research Group, University of Debrecen, 4032 Debrecen, Hungary
2
Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
3
Division of Dental Anatomy, Department of Basic Medical Sciences, Faculty of Dentistry, University of Debrecen, 4032 Debrecen, Hungary
4
Department of Surgery and Cancer, Imperial College London, London SW7 ZAZ, UK
5
Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
*
Author to whom correspondence should be addressed.
Academic Editor: Zsuzsanna Helyes
Int. J. Mol. Sci. 2021, 22(5), 2297; https://doi.org/10.3390/ijms22052297
Received: 8 January 2021 / Revised: 20 February 2021 / Accepted: 21 February 2021 / Published: 25 February 2021
(This article belongs to the Special Issue Molecular Links between Sensory Nerves, Inflammation, and Pain)
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. View Full-Text
Keywords: histone; epigenetic modification; superficial dorsal horn neuron; burn injury; neuropeptides; nociception histone; epigenetic modification; superficial dorsal horn neuron; burn injury; neuropeptides; nociception
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MDPI and ACS Style

Varga, A.; Mészár, Z.; Sivadó, M.; Bácskai, T.; Végh, B.; Kókai, É.; Nagy, I.; Szücs, P. Spinal Excitatory Dynorphinergic Interneurons Contribute to Burn Injury-Induced Nociception Mediated by Phosphorylated Histone 3 at Serine 10 in Rodents. Int. J. Mol. Sci. 2021, 22, 2297. https://doi.org/10.3390/ijms22052297

AMA Style

Varga A, Mészár Z, Sivadó M, Bácskai T, Végh B, Kókai É, Nagy I, Szücs P. Spinal Excitatory Dynorphinergic Interneurons Contribute to Burn Injury-Induced Nociception Mediated by Phosphorylated Histone 3 at Serine 10 in Rodents. International Journal of Molecular Sciences. 2021; 22(5):2297. https://doi.org/10.3390/ijms22052297

Chicago/Turabian Style

Varga, Angelika, Zoltán Mészár, Miklós Sivadó, Tímea Bácskai, Bence Végh, Éva Kókai, István Nagy, and Péter Szücs. 2021. "Spinal Excitatory Dynorphinergic Interneurons Contribute to Burn Injury-Induced Nociception Mediated by Phosphorylated Histone 3 at Serine 10 in Rodents" International Journal of Molecular Sciences 22, no. 5: 2297. https://doi.org/10.3390/ijms22052297

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