title: mTOR pathway is involved in ADP-evoked astrocyte activation and ATP release in the spinal dorsal horn in a rat neuropathic pain model.
abstract: BACKGROUND
  ATP/ADP-evoked spinal astrocyte activation plays a vital role in the development of neuropathic pain. We aim to investigate the role of mammalian target of rapamycin (mTOR) pathway on the spinal astrocyte activation in the neuropathic pain development in rats.
  
  
  METHODS
  Sprague Dawley (SD) rats were subjected to chronic constriction of the sciatic nerve (CCI). Rapamycin or ADP was intrathecally injected daily to explore their effects on spinal astrocyte activation and pain development. Expression of glial fibrillary acidic protein (GFAP) and mTOR in the spinal dorsal horn was assessed by immunohistochemistry. Von Frey hairs and Hargreaves paw withdrawal test were conducted to evaluate mechanical allodynia and thermal sensitivity, respectively. Firefly luciferase ATP assay was used to assess the change of ATP level in cerebrospinal fluid (CSF) and medium of cultured astrocytes.
  
  
  RESULTS
  GFAP expression was enhanced in the ipsilateral spinal dorsal horn from day 3 after surgery. GFAP and mTOR expression in the rat spinal dorsal horn on post-surgical day 14 was enhanced by daily intrathecal injection of ADP, which was inhibited by rapamycin. Rapamycin decreased lower mechanical pain threshold and the thermal withdrawal latency. Intrathecal injection of ADP enhanced the ATP release, which was partially inhibited by rapamycin. Study of cultured astrocytes indicated that ATP could be released from astrocytes.
  
  
  CONCLUSIONS
  Our data demonstrated that ADP enhanced neuropathic pain in CCI rats, which was inhibited by rapamycin. This study indicates that targeting mTOR pathway could serve as a novel therapeutic strategy in neuropathic pain management.
authors: Department of Anaesthesiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: J
authors: J
authors: Cui
authors: Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors: W
authors: W
authors: He
authors: Department of Anaesthesiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: B
authors: B
authors: Yi
authors: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.
authors: H
authors: H
authors: Zhao
authors: Department of Anaesthesiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: lukaizhi2012@hotmail.com.
authors: K
authors: K
authors: Lu
authors: Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China. Electronic address: HuaizR2014@126.com.
authors: H
authors: H
authors: Ruan
authors: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.
authors: D
authors: D
authors: Ma
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D009437:Neuralgia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D066148:Spinal Cord Dorsal Horn / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases
keywords: adenosine diphosphate; adenosine triphosphate; astrocyte; mammalian target of rapamycin; neuropathic pain