Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Gwangju, Korea.
Korean J Anesthesiol. 2013 Oct;65(4):331-6. doi: 10.4097/kjae.2013.65.4.331. Epub 2013 Oct 24.
Thalidomide has been recognized as having an anti-allodynic effect against neuropathic pain induced by spinal nerve ligation. Its clinical beneficial effects are mainly derived from its immune-modulating property, which is known to influence the analgesic action of morphine. The possible characteristics of systemic interactions between thalidomide and morphine in the context of spinal nerve ligation-induced neuropathic pain were examined in rats.
Neuropathic pain was induced by ligation of the L5/6 spinal nerves in male Sprague-Dawley rats and mechanical allodynia was assessed using von Frey filaments. The ED50 was calculated for thalidomide and for morphine, and the mixture of both drugs was intraperitoneally administered at different doses of ED50 of each drug (1/8, 1/4, 1/2, 1/1 of ED50) to obtain the experimental ED50 value for the combination of thalidomide and morphine. Isobolographic analysis was used to evaluate the characteristics of drug interactions between morphine and thalidomide.
The ED50 of thalidomide was three-fold higher than that of morphine. The experimental ED50 value of the mixture of thalidomide and morphine was significantly lower than the calculated theoretical ED50 value. Isobolographic analysis revealed a synergistic interaction for anti-allodynic effect after intraperitoneal delivery of the thalidomide-morphine mixture.
These results suggest that thalidomide acts synergistically with morphine to produce an anti-allodynic effect in neuropathic pain induced by spinal nerve ligation in rats. Thus, the combination of thalidomide with morphine may be one of the useful strategies in the management of neuropathic pain.
沙利度胺已被证实对脊神经结扎诱发的神经性疼痛具有抗痛觉过敏作用。其临床疗效主要源于其免疫调节特性，已知该特性会影响吗啡的镇痛作用。本研究在脊神经结扎诱发的神经性疼痛大鼠模型中，观察了沙利度胺和吗啡全身相互作用的可能特征。
雄性 Sprague-Dawley 大鼠通过结扎 L5/6 脊神经诱发神经性疼痛，采用 von Frey 细丝评估机械性痛觉过敏。计算沙利度胺和吗啡的 ED50，然后以两种药物 ED50 的不同剂量（各药物的 1/8、1/4、1/2、1/1）混合腹腔给药，获得沙利度胺和吗啡联合用药的实验 ED50 值。采用等比图形分析法评价吗啡和沙利度胺之间药物相互作用的特征。
沙利度胺的 ED50 是吗啡的 3 倍。沙利度胺和吗啡混合物的实验 ED50 值明显低于计算的理论 ED50 值。等比图形分析显示，腹腔给予沙利度胺-吗啡混合物后具有抗痛觉过敏的协同相互作用。
这些结果表明，沙利度胺与吗啡联合应用在大鼠脊神经结扎诱发的神经性疼痛中具有协同抗痛觉过敏作用。因此，沙利度胺与吗啡联合应用可能是神经性疼痛治疗的一种有效策略。
