Local resiniferatoxin induces long-lasting analgesia in a rat model of full thickness thermal injury

MM Salas, JL Clifford, JR Hayden, MJ Iadarola… - Pain …, 2017 - academic.oup.com
MM Salas, JL Clifford, JR Hayden, MJ Iadarola, DL Averitt
Pain medicine, 2017academic.oup.com
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 …
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.
Oxford University Press