title: Phosphorylated Histone 3 at Serine 10 Identifies Activated Spinal Neurons and Contributes to the Development of Tissue Injury-Associated Pain.
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.
authors.affiliation: Nociception Group, Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, London, SW10 9NH, United Kingdom.
authors.forename: Jose Vicente
authors.initials: JV
authors.lastname: Torres-Pérez
authors.affiliation: Department of Physiology, University of Szeged, Szeged, H-6720, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Sántha
authors.affiliation: MTA-DE-NAP B-Pain Control Research Group, University of Debrecen, Debrecen, H-4012, Hungary.
authors.forename: Angelika
authors.initials: A
authors.lastname: Varga
authors.affiliation: MTA-DE-NAP B-Pain Control Research Group, University of Debrecen, Debrecen, H-4012, Hungary.|Department of Anatomy, Histology and Embryology, University of Debrecen, Debrecen, H-4012, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Szucs
authors.affiliation: Nociception Group, Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, London, SW10 9NH, United Kingdom.
authors.forename: Joao
authors.initials: J
authors.lastname: Sousa-Valente
authors.affiliation: Department of Anatomy, Histology and Embryology, University of Debrecen, Debrecen, H-4012, Hungary.
authors.forename: Botond
authors.initials: B
authors.lastname: Gaal
authors.affiliation: MTA-DE-NAP B-Pain Control Research Group, University of Debrecen, Debrecen, H-4012, Hungary.|Department of Anatomy, Histology and Embryology, University of Debrecen, Debrecen, H-4012, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Sivadó
authors.affiliation: Nociception Group, Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, London, SW10 9NH, United Kingdom.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Andreou
authors.affiliation: Nociception Group, Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, London, SW10 9NH, United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Beattie
authors.affiliation: The Ipswich Hospital, Ipswich, IP4 5PD, United Kingdom.
authors.forename: Bence
authors.initials: B
authors.lastname: Nagy
authors.affiliation: Department of Anatomy, Histology and Embryology, University of Debrecen, Debrecen, H-4012, Hungary.
authors.forename: Klara
authors.initials: K
authors.lastname: Matesz
authors.affiliation: Division of Cell Signalling and Immunology, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, United Kingdom.
authors.forename: J Simon
authors.initials: JS
authors.lastname: C Arthur
authors.affiliation: Department of Physiology, University of Szeged, Szeged, H-6720, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Jancsó
authors.affiliation: Nociception Group, Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, London, SW10 9NH, United Kingdom.
authors.forename: Istvan
authors.initials: I
authors.lastname: Nagy
mesh_terms: D000818:Animals; D006657:Histones / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D059225:Nociception; D010766:Phosphorylation; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors
chemical_list: D006657:Histones; D047428:Protein Kinase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3