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新型单侧爪切除术模型的初步评估及缓释丁丙诺啡产品的疗效

Pilot evaluation of a novel unilateral onychectomy model and efficacy of an extended release buprenorphine product.

作者信息

Enomoto Masataka, Kigin Patricia D, Bledsoe David, Slone Robyn, Hash Jonathan, Smith Charles E, Lascelles B Duncan X

机构信息

Comparative Pain Research Laboratory Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.

Farnam Companies, Inc., Phoenix, AZ, USA.

出版信息

BMC Vet Res. 2017 Jan 24;13(1):32. doi: 10.1186/s12917-017-0943-5.

Abstract

BACKGROUND

Non-steroidal anti-inflammatory drugs (NSAIDs), transdermal fentanyl patches, and transmucosal buprenorphine are probably the most commonly used options for providing post-operative analgesia in the early at-home period. However, these require daily administration or are associated with abuse concerns. One of the significant unmet needs in veterinary surgery and pain management is for longer acting opioids for cats to effectively bridge the gap between the in-hospital and at-home recovery periods. A proof of concept study of an extended release formulation of buprenorphine HCL (ER-Bup) was conducted using objective kinetic measures and a unilateral onychectomy model. Using a blinded, randomized, two period crossover design, four cats were allocated to control (saline) or ER-Bup (0.6 mg/kg, subcutaneously [SC]) treatment groups. All animals underwent a unilateral forelimb onychectomy per period with a washout/recovery period in between. Observational pain scores and kinetic data (using a pressure sensitive walkway [PSW]) were collected prior to (baseline) and at intervals for 72 h following surgery. Symmetry indices were derived for kinetic variables (peak vertical force [PVF]; vertical impulse [VI]) of each forelimb for landing following a jump and for walking. A rescue analgesic protocol was in place. Effect of surgery and treatment were evaluated using a mixed model statistical approach.

RESULTS

No cats required rescue analgesics based on subjective pain score. ER-Bup had a positive influence on subjective pain scores during the 72 h postsurgery (p = 0.0473). PVF and VI of the operated limb were significantly decreased for both landing (p < 0.0001 and p < 0.0001) and walking (p < 0.0001 and p < 0.0001 respectively) compared to control. ER-Bup resulted in significantly decreased asymmetry in limb use during landing (PVF, p < 0.0001; VI, p < 0.0001) and walking (PVF, p = 0.0002, VI, p < 0.0001). The novel use of data collected following a jump from an elevated platform appeared to provide all desired information and was easier to collect than walking data.

CONCLUSION

This study demonstrates that SC administration of ER-Bup may be an effective analgesic for a 72 h period postoperatively. Furthermore, landing onto a PSW from an elevated perch may be a useful and efficient way to assess analgesics in cats using a unilateral model of limb pain.

摘要

背景

非甾体抗炎药(NSAIDs)、透皮芬太尼贴剂和经黏膜丁丙诺啡可能是在家中早期提供术后镇痛最常用的选择。然而,这些需要每日给药或存在滥用问题。兽医外科手术和疼痛管理中一个尚未满足的重大需求是为猫提供长效阿片类药物,以有效弥合住院和在家恢复阶段之间的差距。使用客观动力学指标和单侧爪切除术模型对盐酸丁丙诺啡缓释制剂(ER - Bup)进行了一项概念验证研究。采用双盲、随机、两阶段交叉设计,将四只猫分配到对照组(生理盐水)或ER - Bup组(0.6mg/kg,皮下注射[SC])。每组动物在每个阶段均接受单侧前肢爪切除术,中间有洗脱/恢复期。在手术前(基线)以及术后72小时内定期收集观察性疼痛评分和动力学数据(使用压力敏感步道[PSW])。计算每只前肢在跳跃着陆和行走时的动力学变量(峰值垂直力[PVF];垂直冲量[VI])的对称指数。制定了救援镇痛方案。采用混合模型统计方法评估手术和治疗的效果。

结果

基于主观疼痛评分,没有猫需要救援镇痛。ER - Bup对术后72小时内的主观疼痛评分有积极影响(p = 0.0473)。与对照组相比,手术肢体在着陆(p < 0.0001和p < 0.0001)和行走(分别为p < 0.0001和p < 0.0001)时的PVF和VI均显著降低。ER - Bup导致着陆(PVF,p < 0.0001;VI,p < 0.0001)和行走(PVF,p = 0.0002,VI,p < 0.0001)时肢体使用的不对称性显著降低。从高架平台跳跃后收集的数据的新用途似乎提供了所有所需信息,并且比行走数据更容易收集。

结论

本研究表明,皮下注射ER - Bup可能是术后72小时有效的镇痛药。此外,从高架栖息处跳到PSW上可能是使用单侧肢体疼痛模型评估猫镇痛药的一种有用且有效的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed3a/5259973/fdf72ef3c2be/12917_2017_943_Fig1_HTML.jpg

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