The effect of epidural resiniferatoxin in the neuropathic pain rat model

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.