Department of Anesthesia, McGill University, Montreal, Quebec, Canada H3G 1Y6.
J Neurochem. 2010 Apr;113(2):552-61. doi: 10.1111/j.1471-4159.2010.06625.x. Epub 2010 Jan 28.
Pregabalin is an anti-convulsant that successfully treats many neuropathic pain syndromes, although the mechanism of its anti-hyperalgesic action remains elusive. This study aims to help delineate pregabalin's anti-hyperalgesic mechanisms. We assessed the effectiveness of pregabalin at decreasing mechanical and cold hypersensitivity induced in a rat model of neuropathic pain. Thus, we compared the effectiveness of pre- or post-treatment with systemic or intrathecal (i.t.) pregabalin at reducing the development and maintenance of the neuropathic pain symptoms. Pregabalin successfully decreased mechanical and cold hypersensitivity, as a pre-treatment, but was less effective at suppressing cold hypersensitivity when administered as a post-treatment. Furthermore, both i.t. and systemic administration of pregabalin were effective in reducing the behavioral hypersensitivity, with the exception of systemic post-treatment on cold hypersensitivity. We also examined pregabalin's effects at inhibiting hind paw formalin-induced nociception in naïve rats and formalin-induced release of excitatory amino acids in the spinal cord dorsal horn (SCDH) both in naïve rats and in rats with neuropathic pain. Pregabalin dose-dependently reduced nociceptive scores in the formalin test. We also present the first evidence that pregabalin reduces the formalin-induced release of glutamate in SCDH. Furthermore, i.t. pregabalin reduces the enhanced noxious stimulus-induced spinal release of glutamate seen in neuropathic rats. These data suggest that pregabalin reduces neuropathic pain symptoms by inhibiting the release of glutamate in the SCDH.
普瑞巴林是一种抗惊厥药物，能成功治疗多种神经性疼痛综合征，但其抗痛觉过敏的作用机制仍不清楚。本研究旨在帮助阐明普瑞巴林的抗痛觉过敏机制。我们评估了普瑞巴林在降低神经性疼痛大鼠模型中机械性和冷敏性的有效性。因此，我们比较了全身或鞘内（i.t.）普瑞巴林预处理或后处理对减轻神经性疼痛症状的发展和维持的效果。普瑞巴林作为预处理可成功降低机械性和冷敏性，但作为后处理时抑制冷敏性的效果较差。此外，鞘内和全身给予普瑞巴林均可有效减轻行为性痛觉过敏，除了全身后处理对冷敏性的影响。我们还研究了普瑞巴林对正常大鼠福尔马林诱导的伤害性感受和正常大鼠及神经性疼痛大鼠脊髓背角（SCDH）中兴奋性氨基酸释放的抑制作用。普瑞巴林剂量依赖性地降低福尔马林试验中的疼痛评分。我们还首次证明普瑞巴林可降低 SCDH 中福尔马林诱导的谷氨酸释放。此外，鞘内给予普瑞巴林可降低神经性疼痛大鼠中增强的有害刺激诱导的脊髓谷氨酸释放。这些数据表明，普瑞巴林通过抑制 SCDH 中谷氨酸的释放来减轻神经性疼痛症状。
