1. 2012;15;287-296The Effect of Epidural Resiniferatoxin in the Neuropathic Pain Rat Model
   Randomized Trial
   Billy K Huh, MD, PhD, Sang Sik Choi, MD, PhD, Dong Kyu Lee, MD, PhD, Mi Geum Lee, MD, PhD, Byung Gun Lim, MD, PhD, and Mikyoung Lee, MD, PhD.

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.