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鞘内注射MK-801与局部神经麻醉协同降低实验性周围单神经病大鼠的伤害性反应行为。

Intrathecal MK-801 and local nerve anesthesia synergistically reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy.

作者信息

Mao J, Price D D, Mayer D J, Lu J, Hayes R L

机构信息

Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.

出版信息

Brain Res. 1992 Apr 3;576(2):254-62. doi: 10.1016/0006-8993(92)90688-6.

Abstract

The hyperalgesia and spontaneous pain that occur following peripheral nerve injury may be related to abnormal peripheral input or altered central activity, or both. The present experiments investigated these possibilities by examining the effects of MK-801 (a non-competitive N-methyl-D-aspartate, NMDA, receptor antagonist) and bupivacaine (a local anesthetic agent) on thermal hyperalgesia and spontaneous nociceptive behaviors in rats with painful peripheral mononeuropathy. Peripheral mononeuropathy was produced by loosely ligating the rat's common sciatic nerve, a procedure which causes chronic constrictive injury (CCI) of the ligated nerve. The resulting hyperalgesia to radiant heat and spontaneous nociceptive behaviors was assessed by using a foot-withdrawal test and a spontaneous pain behavior rating method, respectively. CCI rats receiving 4 daily intraperitoneal (i.p.) MK-801 injections (0.03, 0.1, 0.3 mg/kg) beginning 15 min prior to nerve ligation exhibited less hyperalgesia (i.e., longer foot-withdrawal latencies) on days 3, 5, 7, 10, and 15 after nerve ligation as compared to those receiving saline injections. Thermal hyperalgesia also was reduced when a single MK-801 injection was given intrathecally (i.t.) onto the spinal cord lumbar segments on Day 3 after nerve ligation. This effect of postinjury MK-801 treatment was dose-dependent (2.5-20 nmol) and lasted for at least 48 h after injection. Moreover, i.t. injection of MK-801 (10 nmol) reliably lowered spontaneous pain behavior rating scores in CCI rats compared to those in the saline group. The spinal site of MK-801 action is situated within the caudal (probably lumbar) spinal cord, since i.t. injection of MK-801 (10 nmol) onto the spinal cord thoracic segments did not affect thermal hyperalgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

外周神经损伤后出现的痛觉过敏和自发痛可能与外周输入异常或中枢活动改变有关,或两者皆有关。本实验通过研究MK-801(一种非竞争性N-甲基-D-天冬氨酸,NMDA,受体拮抗剂)和布比卡因(一种局部麻醉剂)对疼痛性外周单神经病大鼠热痛觉过敏和自发伤害性感受行为的影响,来探究这些可能性。通过松散结扎大鼠坐骨神经来制造外周单神经病,该操作会导致结扎神经的慢性压迫性损伤(CCI)。分别使用足部撤离试验和自发疼痛行为评分法评估由此产生的对辐射热的痛觉过敏和自发伤害性感受行为。在神经结扎前15分钟开始,每天腹腔注射4次MK-801(0.03、0.1、0.3mg/kg)的CCI大鼠,与接受盐水注射的大鼠相比,在神经结扎后第3、5、7、10和15天表现出较轻的痛觉过敏(即更长的足部撤离潜伏期)。在神经结扎后第3天,将单次MK-801注射入脊髓腰段时,热痛觉过敏也有所减轻。损伤后MK-801治疗的这种效果呈剂量依赖性(2.5 - 20nmol),且注射后至少持续48小时。此外,与盐水组相比,向CCI大鼠鞘内注射MK-801(10nmol)能可靠地降低自发疼痛行为评分。MK-801的作用脊髓部位位于尾侧(可能是腰段)脊髓,因为向脊髓胸段注射MK-801(10nmol)不影响热痛觉过敏。(摘要截选至250字)

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