title: Improvements in impaired GABA and GAD65/67 production in the spinal dorsal horn contribute to exercise-induced hypoalgesia in a mouse model of neuropathic pain.
abstract: BACKGROUND
  Physical exercise effectively attenuates neuropathic pain, and multiple events including the inhibition of activated glial cells in the spinal dorsal horn, activation of the descending pain inhibitory system, and reductions in pro-inflammatory cytokines in injured peripheral nerves may contribute to exercise-induced hypoalgesia. Since fewer GABAergic hypoalgesic interneurons exist in the dorsal horn in neuropathic pain model animals, the recovery of impaired GABAergic inhibition in the dorsal horn may improve pain behavior. We herein determined whether the production of gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD) in the dorsal horn is restored by treadmill running and contributes to exercise-induced hypoalgesia in neuropathic pain model mice. C57BL/6 J mice underwent partial sciatic nerve ligation (PSL). PSL-Runner mice ran on a treadmill at 7 m/min for 60 min/day, 5 days/week, from two days after PSL.
  
  
  RESULTS
  Mechanical allodynia and heat hyperalgesia developed in PSL-Sedentary mice but were significantly attenuated in PSL-Runner mice. PSL markedly decreased GABA and GAD65/67 levels in neuropils in the ipsilateral dorsal horn, while treadmill running inhibited these reductions. GABA+ neuronal nuclei+ interneuron numbers in the ipsilateral dorsal horn were significantly decreased in PSL-Sedentary mice but not in PSL-Runner mice. Pain behavior thresholds positively correlated with GABA and GAD65/67 levels and GABAergic interneuron numbers in the ipsilateral dorsal horns of PSL-Sedentary and -Runner mice.
  
  
  CONCLUSIONS
  Treadmill running prevented PSL-induced reductions in GAD65/67 production, and, thus, GABA levels may be retained in interneurons and neuropils in the superficial dorsal horn. Therefore, improvements in impaired GABAergic inhibition may be involved in exercise-induced hypoalgesia.
authors.affiliation: Department of Rehabilitation Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan kami@wakayama-med.ac.jp.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Kami
authors.affiliation: Department of Rehabilitation Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Taguchi Ms
authors.affiliation: Department of Rehabilitation Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Tajima
authors.affiliation: Department of Rehabilitation Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan Department of Physical Therapy, Osaka Yukioka College of Health Science, Ibaraki City, Osaka, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Senba
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D017288:Pain Threshold; D010805:Physical Conditioning, Animal; D066148:Spinal Cord Dorsal Horn / Q000201:enzymology* / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2
keywords: Gamma-aminobutyric acid; exercise-induced hypoalgesia; glutamic acid decarboxylase; neuropathic pain; treadmill running