Department of Anesthesiology and Pain Medicine, Gachon University Dongincheon Gil Hospital, Incheon, Korea.
Pain Physician. 2012 Jul-Aug;15(4):287-96.
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.
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.
A randomized, experimental trial.
Department of Anesthesiology and Pain Medicine, Korea University Guro Hospital
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.
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.
A histological examination by electron-microscopic staining was not performed. The observation period was not very long (20 days).
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.
树脂毒素（RTX）是一种对瞬时受体电位香草酸亚型 1（TRPV1）具有高选择性的合成激动剂，具有抗伤害感受作用。硬膜外 RTX 对神经病理性疼痛大鼠模型的镇痛作用尚未得到研究。
本研究旨在评估硬膜外 RTX 对机械和热刺激致神经病理性疼痛大鼠模型的镇痛作用，并研究其剂量相关性行为改变和副作用。
随机、实验性试验。
韩国大学古罗医院麻醉与疼痛医学系
使用雄性 Sprague-Dawley 大鼠（7 周龄，体重 230-250 g）建立脊神经结扎模型。在 L4-L5 水平放置硬膜外导管。每个研究组（n = 6）接受不同剂量的 RTX：100 ng、500 ng、1 μg、2 μg、4 μg 和 10 μg。所有物质均以 20 μL 体积剂量给药。对照组（n = 6）接受 20 μL 生理盐水。我们评估了硬膜外 RTX 注射后短期（3 小时）和长期（20 天）机械和热刺激反应以及镇静评分。
在 RTX 给药后最初 60 分钟内，短暂的剂量依赖性痛觉过敏（500 ng、1 μg）或镇静（>/= 2 μg）先于对热刺激的长时间镇痛。在较高剂量（>/= 2 μg）时，观察到明显的镇静和过度通气，而 6 只大鼠中有 2 只在 10 μg 剂量下死亡。硬膜外 RTX 的 ED50 为 265 ng（95%置信区间 216.1-324.9 ng）。RTX>/=1 μg 时，热刺激潜伏期持续 20 天增加。但机械刺激的阈值仅在急性期增加，并在 3-5 天后恢复基线，与给予的剂量无关。
未进行电子显微镜染色的组织学检查。观察期不是很长（20 天）。
RTX 具有在大鼠神经病理性疼痛模型中以较小剂量经硬膜外途径使用的潜力，可产生短暂改善机械性超敏反应和延长热镇痛反应。
