Phosphorylated Histone 3 at Serine 10 Identifies Activated Spinal Neurons and Contributes to the Development of Tissue Injury-Associated Pain

Jose Vicente Torres-Pérez, Péter Sántha, Angelika Varga, Peter Szucs, Joao Sousa-Valente, Botond Gaal, Miklós Sivadó, Anna P. Andreou, Sara Beattie, Bence Nagy, Klara Matesz, J. Simon C. Arthur, Gábor Jancsó, Istvan Nagy

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Abstract

Transcriptional changes in superficial spinal dorsal horn neurons (SSDHN) are essential in the development and maintenance of prolonged pain. Epigenetic mechanisms including post-translational modifications in histones are pivotal in regulating transcription. Here, we report that phosphorylation of serine 10 (S10) in histone 3 (H3) specifically occurs in a group of rat SSDHN following the activation of nociceptive primary sensory neurons by burn injury, capsaicin application or sustained electrical activation of nociceptive primary sensory nerve fibres. In contrast, brief thermal or mechanical nociceptive stimuli, which fail to induce tissue injury or inflammation, do not produce the same effect. Blocking N-methyl-D-aspartate receptors or activation of extracellular signal-regulated kinases 1 and 2, or blocking or deleting the mitogen-and stress-activated kinases 1 and 2 (MSK1/2), which phosphorylate S10 in H3, inhibit up-regulation in phosphorylated S10 in H3 (p-S10H3) as well as fos transcription, a down-stream effect of p-S10H3. Deleting MSK1/2 also inhibits the development of carrageenan-induced inflammatory heat hyperalgesia in mice. We propose that p-S10H3 is a novel marker for nociceptive processing in SSDHN with high relevance to transcriptional changes and the development of prolonged pain.

Original languageEnglish
Article number41221
JournalScientific reports
Volume7
DOIs
Publication statusPublished - Jan 25 2017

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Torres-Pérez, J. V., Sántha, P., Varga, A., Szucs, P., Sousa-Valente, J., Gaal, B., Sivadó, M., Andreou, A. P., Beattie, S., Nagy, B., Matesz, K., Arthur, J. S. C., Jancsó, G., & Nagy, I. (2017). Phosphorylated Histone 3 at Serine 10 Identifies Activated Spinal Neurons and Contributes to the Development of Tissue Injury-Associated Pain. Scientific reports, 7, [41221]. https://doi.org/10.1038/srep41221