title: Intrathecal injection of fluorocitric acid inhibits the activation of glial cells causing reduced mirror pain in rats.
abstract: BACKGROUND
  Growing evidence has shown that unilateral nerve injury results in pain hypersensitivity in the ipsilateral and contralateral sides respective to the injury site. This phenomenon is known as mirror image pain (MIP). Glial cells have been indicated in the mechanism of MIP; however, it is not clear how glial cells are involved in MIP.
  
  
  METHODS
  To observe phenomenon MIP and the following mechanism, 20 adult male Sprague-Dawley rats (weighing 180-220 g) were separated into two groups: Sham Group (n = 10) and left L5 spinal nerve ligated and sectioned (SNL) group (n = 10). Thermal hyperalgesia and mechanical hypersensitivity were measured for both groups to determine if the SNL model had Mirror image of Pain (MIP). Nav1.7 protein expression in DRG was analyzed using immunohistochemistry and western-blotting. And then to observe the effect of fluorocitrate on MIP, 15 rats were separated into three Groups: Sham Group (n = 5); SNL + FC group: intrathecal injection of Fluorocitric acid(FC) 1 nmol/10 μL (n = 5); SNL + NS group: intrathecal injection of 0.9% Normal Saline (n = 5). Behavior testing, immunocytochemistry, and western-blotting using dorsal root ganglion (DRG) from both sides were then conducted.
  
  
  RESULTS
  The results showed pain hypersensitivity in both hind-paws of the SNL animals, Mechanical tests showed the paw withdrawal threshold dropped from 13.30 ± 1.204 g to 2.57 ± 1.963 g at 14 d as will as the ipsilateral paw thermal withdrawal threshold dropped from 16.5 ± 2.236 s to 4.38 ± 2.544 s at 14 d. Mechanical tests showed the contralateral paw withdrawal threshold dropped from 14.01 ± 1.412 to 4.2 ± 1.789 g at 7d will the thermal withdrawal threshold dropped from 16.8 ± 2.176 s to 7.6 ± 1.517 s at 7d. Nav1.7 expression increased and glial cells actived in bilateral side DRG after SNL compared with sham group. After intrathecal injection of fluorocitrate, the glial cell in bilateral DRG were inhibited and the pain behavior were reversed in both hindpaws too.
  
  
  CONCLUSIONS
  Fluorocitrate can inhibit the activation of glial cells in spinal cord and DRG, and reduce MIP.
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Anatomy, Zhengzhou University, Zhengzhou, 450001 Henan Province China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Anatomy, Zhengzhou University, Zhengzhou, 450001 Henan Province China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Anatomy, Zhengzhou University, Zhengzhou, 450001 Henan Province China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Anatomy, Zhengzhou University, Zhengzhou, 450001 Henan Province China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Anatomy, Zhengzhou University, Zhengzhou, 450001 Henan Province China.
authors.forename: Qingzan
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Anatomy, Zhengzhou University, Zhengzhou, 450001 Henan Province China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Anatomy, Zhengzhou University, Zhengzhou, 450001 Henan Province China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Anatomy, Zhengzhou University, Zhengzhou, 450001 Henan Province China.
authors.forename: Jiannan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Anatomy, Zhengzhou University, Zhengzhou, 450001 Henan Province China.
authors.forename: Puchao
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Anatomy, Zhengzhou University, Zhengzhou, 450001 Henan Province China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zang
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D002951:Citrates / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control; D007278:Injections, Spinal; D008297:Male; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002951:Citrates; D062556:NAV1.7 Voltage-Gated Sodium Channel; C007744:fluorocitrate
keywords: DL-fluorocitric acid; Mirror-image pain; Nav1.7 protein; Satellite glial cells