Nicholson B
Lehigh Valley Hospital Pain Center, Allentown, Pennsylvania 18103, USA.
Acta Neurol Scand. 2000 Jun;101(6):359-71. doi: 10.1034/j.1600-0404.2000.0006a.x.
The development of neuropathic pain involves a series of changes including primary and secondary hyperalgesia, peripheral and central sensitization, and wind-up phenomena. Neurotransmitters play a critical role in this process. For example, glutaminergic subtypes of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and neurokinin prime the N-methyl-D-aspartate (NMDA) receptor by triggering the release of intracellular calcium ions, thus unblocking the magnesium ion plug on the NMDA receptor and allowing Ca2+ influx into the cell. Ca2+ ions acting as secondary messengers initiate protein kinase C activation, phospholipase C and nitric oxide synthetase production, and proto-oncogene expression. The activation of the NMDA receptor thereby increases the responsiveness of the nociceptive system. Anticonvulsant drugs--including carbamazepine, phenytoin, and felbamate--have been used to treat neuropathic pain. Gabapentin is a novel anticonvulsant that may have a unique effect on voltage-dependent Ca2+ channel currents at postsynaptic dorsal horn neurons. Thus, gabapentin may interrupt an entire series of events, not just a single process, that lead to the development of neuropathic pain. Preclinical models of anti-inflammatory and neuropathic pain indicate that gabapentin effectively antagonizes the maintenance of this pain. Additionally, in preemptive surgical models, gabapentin has been shown to prevent the induction of pain. Gabapentin has been shown to be efficacious in numerous smaller clinical studies, case reports, and chart reviews in a variety of neuropathic pain syndromes. Two large multicenter studies, one in postherpetic neuralgia (PHN) and one in diabetic peripheral neuropathy (DPN), support preclinical findings. In the PHN study, patients treated with gabapentin demonstrated a significant difference (P<0.001) in their average daily pain score at endpoint compared to placebo patients. In the DPN trial, mean weekly pain was significantly (P<0.001) different for gabapentin-treated patients compared to placebo-treated patients at endpoint. Consistent with the known side-effect profile of gabapentin, the most common adverse events noted in both studies were dizziness and somnolence. Gabapentin should be considered an important addition to the management of neuropathic pain syndromes.
神经性疼痛的发展涉及一系列变化，包括原发性和继发性痛觉过敏、外周和中枢敏化以及痛觉过敏增强现象。神经递质在这一过程中起关键作用。例如，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）的谷氨酰胺能亚型和神经激肽通过触发细胞内钙离子释放来启动N-甲基-D-天冬氨酸（NMDA）受体，从而解除NMDA受体上的镁离子阻断，使Ca2+流入细胞。作为第二信使的Ca2+离子启动蛋白激酶C激活、磷脂酶C和一氧化氮合酶生成以及原癌基因表达。NMDA受体的激活从而增加伤害性感受系统的反应性。抗惊厥药物——包括卡马西平、苯妥英和非氨酯——已被用于治疗神经性疼痛。加巴喷丁是一种新型抗惊厥药，可能对突触后背角神经元的电压依赖性Ca2+通道电流有独特作用。因此，加巴喷丁可能会中断导致神经性疼痛发展的整个事件系列，而不仅仅是单个过程。抗炎和神经性疼痛的临床前模型表明，加巴喷丁能有效拮抗这种疼痛的维持。此外，在预防性手术模型中，加巴喷丁已被证明可预防疼痛的诱导。在众多针对各种神经性疼痛综合征的较小规模临床研究、病例报告和病历回顾中，加巴喷丁已被证明是有效的。两项大型多中心研究，一项针对带状疱疹后神经痛（PHN），一项针对糖尿病性周围神经病变（DPN），支持了临床前研究结果。在PHN研究中，与安慰剂组患者相比，接受加巴喷丁治疗的患者在终点时的平均每日疼痛评分有显著差异（P<0.001）。在DPN试验中，与安慰剂组患者相比，加巴喷丁治疗组患者在终点时的每周平均疼痛有显著差异（P<0.001）。与加巴喷丁已知的副作用特征一致，两项研究中最常见的不良事件是头晕和嗜睡。加巴喷丁应被视为神经性疼痛综合征治疗的重要补充药物。
