Choi Jin Woo, In Jang Hyeok, Kim Yong Shin, Kang Yoo Jin, Lim Yong Gul, Cho Su Min, Shin Eun Young, Joo Jin Deok
Department of Anesthesiology and Pain Medicine, The Catholic University of Korea, Seoul, Korea.
Korean J Anesthesiol. 2009 Aug;57(2):210-216. doi: 10.4097/kjae.2009.57.2.210.
In addition to causing the loss of voluntary sensory and motor function, spinal cord injury (SCI) often creates a state of central neuropathic pain. Rats given SCI display increases in the activated form of transcription factors ERK 1/2 MAPK and CREB in the spinal cord, which correspond to allodynia in a model of neuropathic pain. This study was conducted to determine if low dose ketamine had an effect on the activation of ERK 1/2 and CREB in the development of neuropathic pain.
This study was conducted to evaluate ERK 1/2 and CREB protein in a sham operated (control) group, neuropathic pain and normal saline (NP + NS) group and neuropathic pain and ketamine (NP + Keta) group. To accomplish this, male Sprague-Dawley rats were anesthetized and then subjected to L5-L6 spinal nerve ligation (SNL, neuropathic rats). The total amounts of ERK 1/2 and CREB protein were then assessed by western blot analysis. In addition, changes in the amounts of ERK 1/2 and CREB mRNA were evaluated by RT-PCR.
There was a significant increase in the amount of ERK 1/2 and CREB in the NP + NS group when compared with the sham group. However, the amount of ERK 1/2 and CREB protein induced due to SNL were significantly reduced by continuous infusion with ketamine in the NP + Keta group.
The results of this study revealed a positive linkage between NMDA receptors and the ERK-CREB signaling pathway. Therefore, NMDA receptors could be the target of future therapeutic approaches. Additionally, the results of the present study provide additional evidence that low dose ketamine effectively prevents and treats central neuropathic pain following SNL.
脊髓损伤（SCI）除了导致自主感觉和运动功能丧失外，还常常引发中枢神经性疼痛状态。给予脊髓损伤的大鼠脊髓中转录因子ERK 1/2 MAPK和CREB的活化形式增加，这与神经性疼痛模型中的痛觉过敏相对应。本研究旨在确定低剂量氯胺酮在神经性疼痛发展过程中是否对ERK 1/2和CREB的活化有影响。
本研究对假手术（对照）组、神经性疼痛加生理盐水（NP + NS）组和神经性疼痛加氯胺酮（NP + Keta）组的ERK 1/2和CREB蛋白进行评估。为此，将雄性Sprague-Dawley大鼠麻醉，然后进行L5-L6脊髓神经结扎（SNL，神经性大鼠）。然后通过蛋白质印迹分析评估ERK 1/2和CREB蛋白的总量。此外，通过RT-PCR评估ERK 1/2和CREB mRNA量的变化。
与假手术组相比，NP + NS组中ERK 1/2和CREB的量显著增加。然而，在NP + Keta组中，连续输注氯胺酮可显著降低由于SNL诱导的ERK 1/2和CREB蛋白量。
本研究结果揭示了NMDA受体与ERK-CREB信号通路之间的正向联系。因此，NMDA受体可能是未来治疗方法的靶点。此外，本研究结果提供了额外的证据，即低剂量氯胺酮可有效预防和治疗SNL后的中枢神经性疼痛。
