Kristensen Jens Dath, Svensson Björn, Gordh Torsten
Department of Anaesthesiology, University Hospital, UppsalaSweden Department of Anatomy, Uppsala University, UppsalaSweden.
Pain. 1992 Nov;51(2):249-253. doi: 10.1016/0304-3959(92)90266-E.
Involvement of the NMDA receptor system in the transmission of nociceptive information, including the development of central sensitization and a wind-up phenomenon, has increased interest in NMDA-receptor antagonists as antinociceptive drugs. This case report describes the use of an NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) in a carefully selected patient with severe and intractable neurogenic pain in her left leg. The pain syndrome had components of a continuous deep pain, an allodynia, and a wind-up-like component, including afterdischarge and spread of painful sensations outside the territory of the injured nerve. After intrathecal (i.t.) administration of 200 nmol of CPP the continuous deep pain component and allodynia were unchanged, but the following 'wind-up' phenomenon with afterdischarge and spread of the pain sensation in the left half of the body was completely abolished. Another 500 nmol of CPP administered over 2 h did not improve pain relief. Pain thresholds for heat and cold stimulation, measured with a Marstock thermostimulator, did not change. There was no effect on blood pressure, heart rate, sensitivity, reflexes, coordination or motor performance. Psychotomimetic ketamine-like side effects developed 4 h after the last injection of CPP and were probably due to rostral spread of CPP. These early experiences with i.t. administration of NMDA-receptor antagonists to humans indicate that the NMDA-receptor system plays an important role in neurogenic pain and that antagonizing this system may be a useful way to obtain better pain control although psychotomimetic side effects due to rostral spread may be a problem.
N-甲基-D-天冬氨酸（NMDA）受体系统参与伤害性信息传递，包括中枢敏化的发展和一种累加现象，这使得人们对NMDA受体拮抗剂作为抗伤害性药物的兴趣增加。本病例报告描述了在一名精心挑选的左腿患有严重顽固性神经源性疼痛的患者中使用NMDA受体拮抗剂3-(2-羧基哌嗪-4-基)丙基-1-膦酸（CPP）的情况。疼痛综合征包括持续性深部疼痛、痛觉过敏和一种类似累加的成分，包括放电后效应和疼痛感觉在受损神经区域之外的扩散。鞘内注射200 nmol CPP后，持续性深部疼痛成分和痛觉过敏没有变化，但随后的“累加”现象，即放电后效应和左侧身体疼痛感觉的扩散完全消失。在2小时内再给予500 nmol CPP并没有改善疼痛缓解情况。用马尔施托克热刺激器测量的热刺激和冷刺激疼痛阈值没有变化。对血压、心率、感觉、反射、协调或运动表现没有影响。在最后一次注射CPP后4小时出现了类似氯胺酮的拟精神病副作用，这可能是由于CPP向头端扩散所致。这些对人类鞘内注射NMDA受体拮抗剂的早期经验表明，NMDA受体系统在神经源性疼痛中起重要作用，拮抗该系统可能是获得更好疼痛控制的一种有用方法，尽管由于向头端扩散引起的拟精神病副作用可能是一个问题。
