Abdi S, Lee D H, Chung J M
Department of Anesthesiology and Critical Care, The Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Anesth Analg. 1998 Dec;87(6):1360-6.
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 IP); 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.
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.
神经病理性疼痛患者的管理具有挑战性。关于常用辅助药物阿米替林（AMI）、加巴喷丁（GBP）和利多卡因（LDC）对动物模型中神经病理性疼痛行为的急性影响，仅有少数报告。因此，本研究的目的是使用神经病理性疼痛大鼠模型，研究AMI、GBP和LDC对机械性异常性疼痛行为体征的急性影响以及这些药物的作用位点。在氟烷全身麻醉下，通过紧密结扎大鼠左侧L5和L6脊神经造成神经病理性损伤。在实验1中，记录基线机械性异常性疼痛数据，并将动物随机分为五组：第1组腹腔注射生理盐水（IP）；第2组腹腔注射AMI（1.5mg/kg IP）；第3组腹腔注射GBP（50mg/kg IP）；第4组静脉输注生理盐水10分钟；第5组静脉输注LDC（10mg/kg）10分钟。在治疗后0.5、1、2和4小时以及1、3和7天重复测量机械性异常性疼痛。在实验2中，大鼠的制备方法与第一个实验相同，在治疗前直至治疗后1小时记录左侧L5束受损传入纤维连续放电的单单位活动。所有动物在手术后7天内均出现神经病理性疼痛行为。所有三种受试药物在治疗后30分钟时就有效地提高了机械性异常性疼痛的阈值，且该效果持续至少1小时。此外，AMI和LDC降低了受损传入纤维的持续放电率，而GBP对这些放电没有影响。我们的研究结果清楚地表明，用AMI、GBP或LDC治疗的大鼠神经病理性疼痛行为有所减轻。最后，LDC的作用位点似乎主要在外周，GBP的作用位点完全在中枢，而AMI的作用位点似乎既有外周成分又有中枢成分。
在本研究中，我们检验了三种常用于治疗神经病理性疼痛的药物的有效性。在这个已建立的大鼠神经病理性疼痛模型中，全身注射阿米替林、加巴喷丁或利多卡因产生了止痛效果，这支持了它们在管理神经病理性疼痛综合征患者中的临床应用。
