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Int J Mol Sci ; 22(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669046

RESUMO

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.


Assuntos
Queimaduras/metabolismo , Histonas/metabolismo , Nociceptividade/fisiologia , Dor/metabolismo , Células do Corno Posterior/metabolismo , Serina/metabolismo , Medula Espinal/metabolismo , Animais , Epigênese Genética , Feminino , Imuno-Histoquímica , Hibridização In Situ , Proteínas com Homeodomínio LIM/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Fator de Transcrição PAX2/metabolismo , Fosforilação , Ratos , Ratos Wistar , Medula Espinal/citologia , Medula Espinal/fisiologia , Fatores de Transcrição/metabolismo
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