The anti-allodynic effects of amitriptyline, gabapentin, and lidocaine in a rat model of neuropathic pain
The anti-allodynic effects of amitriptyline, gabapentin, and lidocaine in a rat model of neuropathic pain
复制标题
DOI：
10.1097/00000539-199812000-00027
复制
发表时间：
1998-12-01
影响因子：
5.7
通讯作者：
Chung, JM
中科院分区：
文献类型：
--
作者：
Abdi, S;Lee, DH;Chung, JM
神经性疼痛患者的管理是具有挑战性的。关于常用辅助药物阿米替林(AMI)、加巴喷丁(GBP)和利多卡因(LDC)对动物模型神经病理性疼痛行为的急性影响的报道很少。因此，这项研究的目的是利用神经病理性疼痛的大鼠模型，研究急性心肌梗死、GBP和LDC对机械性痛觉异常的行为体征的急性影响以及这些药物的作用部位。在氟烷全身麻醉下，结扎大鼠左侧L5、L6脊神经，造成神经病理性损伤。在实验1中，动物随机分为5组：生理盐水(IP)组、急性心肌梗死(AMI)组(1.5 mg/kg TP)、银杏叶提取物(GBP)组(50 mg/kg)、生理盐水输注10min组(4组)、低密度脂蛋白(LDC)组(10 mg/kg静脉输注)10min。分别于治疗后0.5、1、2、4h、1、3、7d复查机械性超敏反应。在实验2中，大鼠与实验1相似，在治疗前和治疗后1h，记录到左侧L5神经束连续发放受损传入纤维的单一单位活动。所有动物在术后7天内均出现神经病理性疼痛行为。3种受试药物均能在治疗后30min有效地提高机械性痛觉超敏反应阈值，且持续时间至少为1h，且AMI和LDC可降低受损传入纤维的持续放电频率，而银杏叶提取物对这些放电无影响。我们的发现清楚地表明，接受急性心肌梗死、GBP或LDC治疗的大鼠的神经病理性疼痛行为有所减轻。最后，LDC的作用部位似乎主要在外周，而GBP的作用部位仅在中枢，而AMI的作用部位似乎既有外周成分，也有中枢成分。在目前的研究中，我们检查了三种常用药物治疗神经病理性疼痛的有效性。全身注射阿米替林、加巴喷丁或利多卡因在建立的大鼠神经病理性疼痛模型中产生了缓解疼痛的效果，这支持了它们在治疗神经病理性疼痛综合征患者方面的临床应用。
The management of patients with neuropathic pain is challenging. There are only a few reports regarding the acute effects of the commonly used adjuvant drugs amitriptyline (AMI), gabapentin (GBP), and lidocaine (LDC) on neuropathic pain behaviors in animal models. Thus, the purpose of this study was to investigate the acute effects of AMI, GBP, and LDC on behavioral signs of mechanical allodynia and the site of action of these drugs using a rat model of neuropathic pain. Under general anesthesia with halothane, neuropathic injury was produced in rats by tightly ligating the left L5 and L6 spinal nerves. In Experiment 1,baseline mechanical allodynia data were recorded, and the animals were randomly divided into five groups: Group 1 received saline intraperitoneally (IP), Group 2 received AMI (1.5 mg/kg TP); Group 3 received GBP (50 mg/kg IP), Group 4 received an IV saline infusion for 10 min, and Group 5 received LDC (10-mg/kg IV infusion) for 10 min. Measurements of mechanical allodynia were repeated 0.5, 1, 2, and 4 h and 1, 3, and 7 days after treatment. In Experiment 2, rats were prepared similarly to the first experiment, and a single unit activity of continuous discharges of injured afferent fibers was recorded from the left L5 fascicles before and until 1 h after treatment. All animals developed neuropathic pain behavior within 7 days after surgery. All three tested drugs were effective in increasing the threshold for mechanical allodynia as early as 30 min after treatment, and the effect lasted for at least 1 h. Furthermore, AMI and LDC reduced the rate of continuing discharges of injured afferent fibers, whereas GBP did not influence these discharges. Our findings clearly demonstrate an attenuation of neuropathic pain behavior in rats treated with AMI, GBP, or LDC. Finally, the site of action of LDC seems to be primarily in the periphery, and that of GBP is exclusively central, whereas that of AMI seems to have both peripheral and central components. Implications: In the present study, we examined the effectiveness of three drugs commonly used for the treatment of neuropathic pain. Systemic injections of amitriptyline, gabapentin, or lidocaine produced pain-relieving effects in this established model for neuropathic pain in rats, which supports their clinical use in managing patients with neuropathic pain syndromes.