The effect of epidural resiniferatoxin in the neuropathic pain rat model

Mi Geum Lee, Billy K. Huh, Sang Sik Choi, Dong Kyu Lee, Byung Gun Lim, Mi Kyoung Lee

Research output: Contribution to journalArticle

14 Citations (Scopus)

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. Objectives: 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. Study design: A randomized, experimental trial. Setting: 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. Limitations: A histological examination by electron-microscopic staining was not performed. The observation period was not very long (20 days). Conclusion: 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.

Original languageEnglish
Pages (from-to)287-296
Number of pages10
JournalPain Physician
Volume15
Issue number4
Publication statusPublished - 2012

Keywords

  • Epidural administration
  • Mechanical allodynia
  • Mechanical hypersensitivity
  • Resiniferatoxin
  • Sedation
  • Spinal nerve ligation rat model
  • Thermal hyperalgesia

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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    Lee, M. G., Huh, B. K., Choi, S. S., Lee, D. K., Lim, B. G., & Lee, M. K. (2012). The effect of epidural resiniferatoxin in the neuropathic pain rat model. Pain Physician, 15(4), 287-296.