Codd Ellen E, Martinez Rebecca P, Molino Lory, Rogers Kathryn E, Stone Dennis J, Tallarida Ronald J
Research and Early Development, Johnson & Johnson Pharmaceutical Research and Development, PO Box 776, Spring House, PA 19477, USA Temple University School of Medicine, Philadelphia, PA, USA.
Pain. 2008 Feb;134(3):254-262. doi: 10.1016/j.pain.2007.04.019. Epub 2007 May 25.
Neuropathic pain results from injury or dysfunction of the central or peripheral nervous system. The treatment of neuropathic pain is challenging, in part because of its multiple etiologies. The present study explores combinations of the analgesic tramadol and each of four anticonvulsants in the treatment of surgically induced (ligation of the L5 spinal nerve) allodynia in rats. Each of the five drugs studied exhibited a dose-dependent antiallodynic effect. When studied in combination, tramadol and each of two of the anticonvulsants (topiramate and RWJ-333369) interacted synergistically at all three ratios studied, whereas tramadol and each of the other two anticonvulsants (gabapentin and lamotrigine) exhibited a synergistic antiallodynic effect at only one of three ratios investigated. In addition, tramadol and topiramate were found to interact synergistically in a nociceptive pain model, the mouse hot-plate test. These studies suggest the benefit of using combinations of analgesics and anticonvulsants in the relief of neuropathic pain.
神经性疼痛源于中枢或外周神经系统的损伤或功能障碍。神经性疼痛的治疗颇具挑战性，部分原因在于其病因多样。本研究探讨了镇痛药曲马多与四种抗惊厥药分别联合使用，对大鼠手术诱导（L5脊神经结扎）性痛觉过敏的治疗效果。所研究的五种药物均呈现剂量依赖性抗痛觉过敏作用。联合研究时，曲马多与两种抗惊厥药（托吡酯和RWJ - 333369）在所有研究的三种比例下均产生协同作用，而曲马多与另外两种抗惊厥药（加巴喷丁和拉莫三嗪）仅在研究的三种比例中的一种下表现出协同抗痛觉过敏作用。此外，在伤害性疼痛模型小鼠热板试验中，发现曲马多和托吡酯具有协同作用。这些研究表明联合使用镇痛药和抗惊厥药有助于缓解神经性疼痛。
