title: Inhibiting spinal neuron-astrocytic activation correlates with synergistic analgesia of dexmedetomidine and ropivacaine.
abstract: BACKGROUND
  This study aims to identify that intrathecal (i.t.) injection of dexmedetomidine (Dex) and ropivacaine (Ropi) induces synergistic analgesia on chronic inflammatory pain and is accompanied with corresponding "neuron-astrocytic" alterations.
  
  
  METHODS
  Male, adult Sprague-Dawley rats were randomly divided into sham, control and i.t. medication groups. The analgesia profiles of i.t. Dex, Ropi, and their combination detected by Hargreaves heat test were investigated on the subcutaneous (s.c.) injection of complete Freund adjuvant (CFA) induced chronic pain in rat and their synergistic analgesia was confirmed by using isobolographic analysis. During consecutive daily administration, pain behavior was daily recorded, and immunohistochemical staining was applied to investigate the number of Fos-immunoreactive (Fos-ir) neurons on hour 2 and day 1, 3 and 7, and the expression of glial fibrillary acidic protein (GFAP) within the spinal dorsal horn (SDH) on day 1, 3, 5 and 7 after s.c. injection of CFA, respectively, and then Western blot to examine spinal GFAP and β-actin levels on day 3 and 7.
  
  
  RESULTS
  i.t. Dex or Ropi displayed a short-term analgesia in a dose-dependent manner, and consecutive daily administrations of their combination showed synergistic analgesia and remarkably down-regulated neuronal and astrocytic activations indicated by decreases in the number of Fos-ir neurons and the GFAP expression within the SDH, respectively.
  
  
  CONCLUSIONS
  i.t. co-delivery of Dex and Ropi shows synergistic analgesia on the chronic inflammatory pain, in which spinal "neuron-astrocytic activation" mechanism may play an important role.
authors.affiliation: Department of Anesthesiology, Fuzhou General Hospital of Nanjing Military Region, Fuzhou, PR China.
authors.forename: Huang-Hui
authors.initials: HH
authors.lastname: Wu
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Jun-Bin
authors.initials: JB
authors.lastname: Yin
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Cui
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, Fuzhou General Hospital of Nanjing Military Region, Fuzhou, PR China.
authors.forename: Guo-Zhong
authors.initials: GZ
authors.lastname: Chen
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi'an, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000577:Amides / Q000008:administration & dosage*; D000698:Analgesia / Q000379:methods; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D059350:Chronic Pain / Q000188:drug therapy; D020927:Dexmedetomidine / Q000008:administration & dosage*; D004357:Drug Synergism; D005620:Freund's Adjuvant; D005904:Glial Fibrillary Acidic Protein; D007278:Injections, Spinal; D008297:Male; D009474:Neurons / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects
chemical_list: D000577:Amides; D005904:Glial Fibrillary Acidic Protein; D020927:Dexmedetomidine; D000077212:Ropivacaine; D005620:Freund's Adjuvant