Elsevier

The Journal of Pain

Volume 17, Issue 5, May 2016, Pages 588-599
The Journal of Pain

Original Report
Histone Acetylation in Microglia Contributes to Exercise-Induced Hypoalgesia in Neuropathic Pain Model Mice

https://doi.org/10.1016/j.jpain.2016.01.471Get rights and content
Under an Elsevier user license
open archive

Highlights

  • We examined the mechanism of exercise-induced hypoalgesia.

  • Treadmill-running attenuated pain behaviors in neuropathic pain model mice.

  • Treadmill-running increased the number of microglia with acetylated histone H3K9.

  • Epigenetic modification in microglia may contribute to exercise-induced hypoalgesia.

Abstract

Physical exercise can attenuate neuropathic pain (NPP), but the exact mechanism underlying exercise-induced hypoalgesia (EIH) remains unclear. Recent studies have shown that histone hyperacetylation via pharmacological inhibition of histone deacetylases in the spinal cord attenuates NPP, and that histone acetylation may lead to the production of analgesic factors including interleukin 10. We intended to clarify whether histone acetylation in microglia in the spinal dorsal horn contributes to EIH in NPP model mice. C57BL/6J mice underwent partial sciatic nerve ligation (PSL) and PSL- and sham-runner mice ran on a treadmill at a speed of 7 m/min for 60 min/d, 5 days per week, from 2 days after the surgery. PSL-sedentary mice developed mechanical allodynia and heat hyperalgesia, but such behaviors were significantly attenuated in PSL-runner mice. In immunofluorescence analysis, PSL surgery markedly increased the number of histone deacetylase 1-positive/CD11b-positive microglia in the ipsilateral superficial dorsal horn, and they were significantly decreased by treadmill-running. Moreover, the number of microglia with nuclear expression of acetylated H3K9 in the ipsilateral superficial dorsal horn was maintained at low levels in PSL-sedentary mice, but running exercise significantly increased them. Therefore, we conclude that the epigenetic modification that causes hyperacetylation of H3K9 in activated microglia may play a role in producing EIH.

Perspective

This article presents the importance of epigenetic modification in microglia in producing EIH. The current research is not only helpful for developing novel nonpharmacological therapy for NPP, but will also enhance our understanding of the mechanisms and availability of exercise in our daily life.

Key words

Neuropathic pain
exercise-induced hypoalgesia
treadmill-running
histone deacetylase 1
acetylated histone H3K9

Cited by (0)

This study was supported by Grants-in-Aid for Scientific Research C (24500604: K.K.) and B (24390151: E.S.) of the Japan Society for the Promotion of Science. In addition, this study was also supported by a Grant-in-Aid (N46: S.T.) from the Japanese Physical Therapy Association.

The authors have no conflicts of interest to declare.