title: Local Resiniferatoxin Induces Long-Lasting Analgesia in a Rat Model of Full Thickness Thermal Injury.
abstract: OBJECTIVE
  Opioid-based analgesics are a major component of the lengthy pain management of burn patients, including military service members, but are problematic due to central nervous system-mediated side effects. Peripheral analgesia via targeted ablation of nociceptive nerve endings that express the transient receptor potential vanilloid channel 1 (TRPV1) may provide an improved approach. We hypothesized that local injection of the TRPV1 agonist resiniferatoxin (RTX) would produce long-lasting analgesia in a rat model of pain associated with burn injury.
  
  
  METHODS
  Baseline sensitivities to thermal and mechanical stimuli were measured in male and female Sprague-Dawley rats. Under anesthesia, a 100 °C metal probe was placed on the right hind paw for 30 seconds, and sensitivity was reassessed 72 hours following injury. Rats received RTX (0.25 μg/100 μL; ipl) into the injured hind paw, and sensitivity was reassessed across three weeks. Tissues were collected from a separate group of rats at 24 hours and/or one week post-RTX for pathological analyses of the injured hind paw, dorsal spinal cord c-Fos, and primary afferent neuropeptide immunoreactivity.
  
  
  RESULTS
  Local RTX reversed burn pain behaviors within 24 hours, which lasted through recovery at three weeks. At one week following RTX, decreased c-Fos and primary afferent neuropeptide immunoreactivities were observed in the dorsal horn, while plantar burn pathology was unaltered.
  
  
  CONCLUSIONS
  These results indicate that local RTX induces long-lasting analgesia in a rat model of pain associated with burn. While opioids are undesirable in trauma patients due to side effects, RTX may provide valuable long-term, nonopioid analgesia for burn patients.
authors: Pain Management Research Area, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
authors: Margaux M
authors: MM
authors: Salas
authors: Pain Management Research Area, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
authors: John L
authors: JL
authors: Clifford
authors: Pain Management Research Area, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
authors: Jessica R
authors: JR
authors: Hayden
authors: Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors: Michael J
authors: MJ
authors: Iadarola
authors: Department of Biology, Texas Woman's University, Denton, Texas, USA.
authors: Dayna L
authors: DL
authors: Averitt
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002056:Burns / Q000150:complications*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D008297:Male; D059408:Pain Management / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000819:agonists
chemical_list: D000700:Analgesics; D004224:Diterpenes; D050916:TRPV Cation Channels; C024353:resiniferatoxin
keywords: Burn; CGRP; Opioid Sparing; Opioids; Peripheral Analgesia; Resiniferatoxin; Spinal Cord; Substance P; TRPV1; c-Fos