Pharmacological characterisation of a rat model of incisional pain
Pharmacological characterisation of a rat model of incisional pain
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DOI：
10.1038/sj.bjp.0705568
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发表时间：
2004-01-01
影响因子：
7.3
通讯作者：
Walker, K
中科院分区：
文献类型：
--
作者：
Whiteside, GT;Harrison, J;Walker, K
1 术后疼痛的临床和临床前模型在新化学实体的早期评估中得到更频繁的使用。为了评估大鼠切口后疼痛模型的有效性和可靠性，针对多个行为终点评估了不同类别的临床有效镇痛药物的效果。2在全身麻醉下，对大鼠后爪足底表面进行手术切口后，我们使用！分别采用 Randall-Selitto（爪压）测定、电子 von Frey 和双通道体重平均器。行为评估在手术后 24 小时开始，持续 9-14 天。3 手术后 1 天内，患肢出现机械性痛觉过敏、触觉异常性疼痛和负重减轻，术后 1-3 天出现最大敏感性。因此，我们检查了非甾体类抗炎药 (NSAID)、吗啡和加巴喷丁对足底切口 1 天后已确定的痛觉过敏和异常性疼痛的影响。 4 根据之前的报道，全身吗啡和加巴喷丁给药均逆转了切口大鼠后爪的机械性痛觉过敏和触觉异常性疼痛。两种药物对抗机械性痛觉过敏的效果均优于触觉异常性疼痛。5 测试的所有 NSAID 均包括环加氧酶 2 选择性抑制剂、逆转机械性痛觉过敏和大鼠切开后爪的触觉异常性疼痛。对痛觉过敏和异常性疼痛的效力排序为吲哚美辛 > 塞来昔布 > 依托考昔 > 萘普生。6 我们研究了不同类别镇痛药物在大鼠切口后疼痛模型中的效力和功效。这些药物的效力排名反映了它们在临床治疗术后疼痛中的效用。由于这些化合物在两个不同的行为终点（Randall-Selitto（爪压）测定和电子 von Frey）中显示出可靠的功效，因此这些方法可能在手术后疼痛的研究和新疗法的评估中有用。
1 Both clinical and preclinical models of postsurgical pain are being used more frequently in the early evaluation of new chemical entities. In order to assess the validity and reliability of a rat model of postincisional pain, the effects of different classes of clinically effective analgesic drugs were evaluated against multiple behavioural end points.2 Following surgical incision, under general anaesthesia, of the plantar surface of the rat hind paw, we determined flee time course of mechanical hyperalgesia, tactile allodynia and hind limb weight bearing using! the Randall-Selitto (paw pressure) assay, electronic von Frey and dual channel weight averager, respectively. Behavioural evaluations began 24 h following surgery, and were continued for 9-14 days.3 Mechanical hyperalgesia, tactile allodynia and a decrease in weight bearing were present on the affected limb within 1 day of surgery with maximum sensitivity 1-3 days postsurgery. Accordingly, we examined the effect of nonsteroidal antiinflammatory drugs (NSAIDs), morphine and gabapentin, on established hyperalgesia and allodynia, 1 day following plantar incision.4 In accordance with previous reports, both systemic morphine and gabapentin administration reversed mechanical hyperalgesia and tactile allodynia in the incised rat hind paw. Both drugs were more potent against mechanical hyperalgesia than tactile allodynia.5 All of the NSAIDs tested, including cyclooxygenase 2 selective inhibitors, reversed mechanical hyperalgesia and tactile allodynia in the incised rat hind paw. The rank order of potency for both hyperalgesia and allodynia was indomethacin > celecoxib > etoricoxib > naproxen.6 We have investigated the potency and efficacy of different classes of analgesic drugs in a rat model of postincisional pain. The rank order of potency for these drugs reflects their utility in treating postoperative pain in the clinic. As these compounds showed reliable efficacy across two different behavioural end points, the Randall-Selitto (paw pressure) assay and electronic von Frey, these methods may prove useful in the study of postsurgical pain and the assessment of novel treatments.