title: Histone Acetylation in Microglia Contributes to Exercise-Induced Hypoalgesia in Neuropathic Pain Model Mice.
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.
  
  
  
  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.
authors: Department of Rehabilitation Medicine, Wakayama Medical University, Wakayama, Japan. Electronic address: kami@wakayama-med.ac.jp.
authors: Katsuya
authors: K
authors: Kami
authors: Department of Rehabilitation Medicine, Wakayama Medical University, Wakayama, Japan.
authors: Satoru
authors: S
authors: Taguchi
authors: Department of Rehabilitation Medicine, Wakayama Medical University, Wakayama, Japan.
authors: Fumihiro
authors: F
authors: Tajima
authors: Department of Rehabilitation Medicine, Wakayama Medical University, Wakayama, Japan; Department of Physical Therapy, Osaka Yukioka College of Health Science, Osaka, Japan.
authors: Emiko
authors: E
authors: Senba
mesh_terms: D000107:Acetylation; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D005080:Exercise Test; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006930:Hyperalgesia / Q000209:etiology* / Q000473:pathology*; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D010147:Pain Measurement; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000009:adverse effects*; D010812:Physical Stimulation; D020426:Sciatic Neuropathy / Q000503:physiopathology / Q000534:rehabilitation*; D018709:Statistics, Nonparametric
chemical_list: D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D006657:Histones; D016753:Interleukin-10; D056284:Histone Deacetylase 1; D010751:Phosphopyruvate Hydratase
keywords: Neuropathic pain; acetylated histone H3K9; exercise-induced hypoalgesia; histone deacetylase 1; treadmill-running