The effect of epidural resiniferatoxin in the neuropathic pain rat model.

Published

Journal Article

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.

Full Text

Cited Authors

  • Lee, MG; Huh, BK; Choi, SS; Lee, DK; Lim, BG; Lee, M

Published Date

  • July 2012

Published In

Volume / Issue

  • 15 / 4

Start / End Page

  • 287 - 296

PubMed ID

  • 22828682

Pubmed Central ID

  • 22828682

Electronic International Standard Serial Number (EISSN)

  • 2150-1149

International Standard Serial Number (ISSN)

  • 1533-3159

Language

  • eng