title: A pan-caspase inhibitor reduces myocyte apoptosis and neuropathic pain in rats with chronic constriction injury of the sciatic nerve.
abstract: BACKGROUND
  Chronic constriction injury is a widely used model for neuropathic pain in rats. It presents with symptoms resembling human neuropathic pain, such as spontaneous pain, hyperalgesia, and allodynia. Recently, myocyte apoptosis was found in neuropathic rats as a possible promoter of pain and motor dysfunction. Our aim in this study was to demonstrate whether muscle cell apoptosis contributes to neuropathic pain in this animal model.
  
  
  METHODS
  To clarify this issue, we examined pain, nutritive perfusion, and inflammation in muscle tissue as well as myocyte apoptosis in rats with neuropathic pain established by chronic constriction injury of the sciatic nerve. Animals received either the pan-caspase inhibitor zVAD (OMe)-fmk (n = 5) or equivalent volumes of vehicle (n = 6). Sham-operated rats served as controls (n = 6).
  
  
  RESULTS
  At day 4 after nerve ligation, there were no signs of perfusion failure or muscle tissue inflammation in all experimental groups. However, animals treated with the vehicle had marked myocyte apoptosis, which was found almost completely blocked in zVA-Dtreated animals. The zVA-Dtreated animals presented with a significant reduction of pain upon heat, cold, and mechanical stimulation comparable with values found in sham controls.
  
  
  CONCLUSIONS
  Myocyte apoptosis possibly contributes to thermal and mechanical allodynia in this experimental model for neuropathic pain. The development of neuropathic pain symptoms did not depend on disturbances in microcirculation or muscle tissue inflammation.
authors.affiliation: Department of Traumatology and Reconstructive Surgery, University of Rostock, Rostock, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Gradl
authors.forename: Philipp
authors.initials: P
authors.lastname: Herlyn
authors.forename: Burkhard
authors.initials: B
authors.lastname: Finke
authors.forename: Philip
authors.initials: P
authors.lastname: Gierer
authors.forename: Andreas
authors.initials: A
authors.lastname: Wree
authors.forename: Martin
authors.initials: M
authors.lastname: Witt
authors.forename: Thomas
authors.initials: T
authors.lastname: Mittlmeier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vollmar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D061945:Caspase Inhibitors / Q000494:pharmacology*; D003251:Constriction, Pathologic / Q000188:drug therapy* / Q000473:pathology*; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D005727:Ganglia, Spinal / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D032342:Muscle Cells / Q000187:drug effects*; D009437:Neuralgia / Q000188:drug therapy* / Q000473:pathology*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000473:pathology*; D012881:Skin Temperature / Q000187:drug effects
chemical_list: D061945:Caspase Inhibitors