Kim Junesun, Kim Jung Hoon, Kim Youngkyung, Cho Hwi-young, Hong Seung Kil, Yoon Young Wook
Department of Physical Therapy, Korea University College of Health Science, Seoul, Republic of Korea.
Neurosci Lett. 2009 Oct 25;462(3):303-7. doi: 10.1016/j.neulet.2009.07.042. Epub 2009 Jul 18.
In the present study we determined whether spinal cholecystokinin (CCK) or the cholecystokinin receptor is involved in below-level neuropathic pain of spinal cord injury (SCI). The effect of the CCK(B) receptor antagonist, CI-988 on mechanical allodynia and the expression level of CCK and CCK(B) receptor were investigated. Spinal hemisection was done at the T13 level in rats under enflurane anesthesia. CI-988 was administered intraperitoneally and intrathecally and behavioral tests were conducted. After systemic injection, mechanical allodynia was reduced by higher doses of CI-988 (10 and 20mg/kg). Intrathecal CI-988 (100, 200 and 500 microg) dose-dependently increased the paw withdrawal threshold in both paws. Following spinal hemisection, CCK mRNA expression increased on the ipsilateral side at the spinal segments caudal to the injury and both sides of the spinal L4-5 segments without any significant changes in CCK(B) receptor mRNA levels. These results suggest that up-regulation of spinal CCK may contribute to maintenance of mechanical allodynia following SCI and that clinical application of CI-988 or similar drugs may be useful therapeutic agents for management of central neuropathic pain.
在本研究中，我们确定脊髓胆囊收缩素（CCK）或胆囊收缩素受体是否参与脊髓损伤（SCI）平面以下的神经性疼痛。研究了CCK（B）受体拮抗剂CI-988对机械性异常性疼痛以及CCK和CCK（B）受体表达水平的影响。在异氟烷麻醉下对大鼠进行T13节段的脊髓半横切术。腹腔内和鞘内注射CI-988并进行行为测试。全身注射后，较高剂量的CI-988（10和20mg/kg）可减轻机械性异常性疼痛。鞘内注射CI-988（100、200和500μg）剂量依赖性地增加双足的爪撤离阈值。脊髓半横切术后，损伤平面以下脊髓节段的同侧以及脊髓L4-5节段的两侧CCK mRNA表达增加，而CCK（B）受体mRNA水平无任何显著变化。这些结果表明，脊髓CCK的上调可能有助于SCI后机械性异常性疼痛的维持，并且CI-988或类似药物的临床应用可能是治疗中枢神经性疼痛的有效治疗药物。
