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Pain Physician. 2012 Jul-Aug;15(4):287-96.

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

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  • 1Department of Anesthesiology and Pain Medicine, Gachon University Dongincheon Gil Hospital, Incheon, Korea.

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.

PMID:
22828682
[PubMed - indexed for MEDLINE]
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