title: The effect of epidural resiniferatoxin in the neuropathic pain rat model.
abstract: BACKGROUND
  Resiniferatoxin (RTX) is a potent synthetic agonist for transient receptor potential vanilloid subtype 1 (TRPV1), which has a selectivity for antinociception. The analgesic effect of epidural RTX in a rat model of neuropathic pain has not yet been studied.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the analgesic effect of epidural RTX on neuropathic pain in a rat model to mechanical and thermal stimulation. The dose-related behavior changes and side effects were also studied.
  
  
  METHODS
  A randomized, experimental trial.
  
  
  METHODS
  Department of Anesthesiology and Pain Medicine, Korea University Guro Hospital
  
  
  METHODS
  A spinal nerve ligation model was prepared using male Sprague-Dawley rats (7 weeks old, weight 230-250 g). An epidural catheter was placed at the L4-L5 level. Each study group (n = 6) received a different dose of RTX: 100 ng, 500 ng, 1 μg, 2 μg, 4 μg and 10 μg. All substances were administered in 20 μL volume doses. The control group (n = 6) received 20 μL of normal saline. We evaluated the response to mechanical and thermal stimuli as well as the sedation score at both short-term (3 hours) and long-term (20 days) after the epidural RTX injection.
  
  
  RESULTS
  Prolonged analgesia to thermal stimulation was preceded by a transient dose-dependent hyperalgesia (500 ng, 1 μg) or sedation (>/= 2 μg) during the initial 60 minutes after RTX administration. Marked sedation and hyperventilation were noted at higher doses (>/= 2 μg), while 2 out of 6 rats died with a 10 μg dose. ED50 for epidural RTX was 265 ng (95% confidence interval 216.1-324.9 ng). The increased latency to thermal stimulation continued for 20 days at RTX >/=1 μg. But the threshold to mechanical stimulation increased only in the acute period and returned to the baseline after 3-5 days, regardless of the administered dose.
  
  
  CONCLUSIONS
  A histological examination by electron-microscopic staining was not performed. The observation period was not very long (20 days).
  
  
  CONCLUSIONS
  RTX has potential to be used in an epidural route for neuropathic pain in a rat model with a relatively small amount, which produces transitory improvement of mechanical hypersensitivity and prolonged thermal analgesic response.
authors: Department of Anesthesiology and Pain Medicine, Gachon University Dongincheon Gil Hospital, Incheon, Korea.
authors: Mi Geum
authors: MG
authors: Lee
authors: Billy K
authors: BK
authors: Huh
authors: Sang Sik
authors: SS
authors: Choi
authors: Dong Kyu
authors: DK
authors: Lee
authors: Byung Gun
authors: BG
authors: Lim
authors: Mikyoung
authors: M
authors: Lee
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D006930:Hyperalgesia / Q000188:drug therapy; D007268:Injections, Epidural; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D004224:Diterpenes; D009498:Neurotoxins; C024353:resiniferatoxin