Sung Backil, Wang Ging Kuo
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Neurosci Lett. 2004 Mar 4;357(2):115-8. doi: 10.1016/j.neulet.2003.12.048.
We assessed if derivatives of amitriptyline could alleviate mechanical allodynia in a rat model of neuropathic pain. N-methyl amitriptyline (NMA), and amitriptyline HCl (AHC) were compared to evaluate the antiallodynic effects produced by systemic and peripheral administration. Under general anesthesia with halothane, neuropathic injury was produced in rats by tightly ligating the left L5 and L6 spinal nerves. All animals developed neuropathic pain behaviors within 7 days after the surgery. For systemic delivery, three groups of rats were injected intraperitoneally with NMA (15 mg/kg), AHC (12.5 mg/kg), or saline. For peripheral routes of injection, rats were divided into 3 x 3 groups and injected with 100, 330, and 1000 nmol/kg doses of each NMA, AHC and 0.9% normal saline. NMA and AHC suppressed mechanical allodynia following peripheral administration but not following intraperitoneal injection. NMA was less potent but showed a longer-acting response than AHC. This study shows that NMA can be used to relieve mechanical allodynia and is a longer-acting agent than AHC.
我们评估了阿米替林衍生物是否能减轻神经性疼痛大鼠模型中的机械性异常性疼痛。比较了N-甲基阿米替林（NMA）和盐酸阿米替林（AHC），以评估全身给药和外周给药产生的抗异常性疼痛作用。在氟烷全身麻醉下，通过紧密结扎大鼠左侧L5和L6脊神经造成神经性损伤。所有动物在手术后7天内均出现神经性疼痛行为。对于全身给药，三组大鼠分别腹腔注射NMA（15毫克/千克）、AHC（12.5毫克/千克）或生理盐水。对于外周注射途径，大鼠分为3×3组，分别注射100、330和1000纳摩尔/千克剂量的NMA、AHC和0.9%生理盐水。外周给药后，NMA和AHC可抑制机械性异常性疼痛，但腹腔注射后则无此作用。NMA的效力较低，但比AHC的作用持续时间更长。本研究表明，NMA可用于缓解机械性异常性疼痛，且是一种比AHC作用持续时间更长的药物。
