Inhibiting spinal neuron-astrocytic activation correlates with synergistic analgesia of dexmedetomidine and ropivacaine

• Published in: PloS one 2014-03, Vol.9 (3), p.e92374
• Main Authors: Wu, Huang-Hui, Yin, Jun-Bin, Zhang, Ting, Cui, Yuan-Yuan, Dong, Yu-Lin, Chen, Guo-Zhong, Wang, Wen
• Format: Article
• Language: English
• Subjects: Actin; Activation; Amides - administration & dosage; Analgesia; Analgesia - methods; Analgesics; Anesthesia; Anesthesiology; Animals; Astrocytes - drug effects; Brain research; Chronic pain; Chronic Pain - drug therapy; Dexmedetomidine - administration & dosage; Dorsal horn; Drug dosages; Drug Synergism; Drugs; Embryology; Freund's Adjuvant; Glial Fibrillary Acidic Protein; Histology; Hyperalgesia; Immunohistochemistry; Inflammation; Injection; Injections, Spinal; Intermediate filament proteins; Kinases; Male; Medical research; Medicine; Medicine and Health Sciences; Muscle proteins; Neurons; Neurons - drug effects; Pain; Pain perception; Pharmaceuticals; Pharmacology; Rats; Rats, Sprague-Dawley; Rodents; Ropivacaine; Spinal Cord Dorsal Horn - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0092374

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. 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. 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. 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.