Transcriptional changes in
superficial spinal dorsal horn neurons (SSDHN) are
essential in the development and maintenance of prolonged pain. Epigenetic
mechanisms including post-translational mo
difications in histones are pivotal in
regulating transcription. Here, we report th
at 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 signa
l-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.