Sun Yu-E, Lu Cui-E, Lei Yishan, Liu Yue, Ma Zhengliang, Gu Xiaoping
Department of Anaesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University Nanjing 210008, Jiangsu Province, China.
Int J Clin Exp Med. 2015 Nov 15;8(11):20178-87. eCollection 2015.
The aim of this study is to investigate the effects of Mas-related G-protein-coupled receptor C (MrgC) agonist bovine adrenal medulla 8-22 (BAM8-22) on bone cancer pain and mirror-image pain.
Bone cancer pain was induced by intramedullary injection of NC2472 fibrosarcoma cells in the mice. BAM8-22 and/or anti-MrgC antibody were injected intrathecally at day 14 after bone cancer induction and their effects on pain behaviors were detected. The pain behaviours were assessed by the number of spontaneous foot lifts and paw withdrawal mechanical threshold (PWMT) tests. MrgC expression was detected using western blot analysis and immunofluorescence assay.
There were increased bone cancer pain and mirror-image pain in the tumor-bearing mice while not in the sham-treated mice. BAM8-22 attenuated bone cancer pain in mice dose dependently with the highest effects at 2 hr after BAM8-22 administration, and anti-MrgC antibody reversed the effects of BAM8-22. However, intrathecal administration of BAM8-22 did not affect the mirror-image pain. Furthermore, BAM8-22 stimulated the expression of MrgC in the spinal dorsal horn.
MrgC agonist BAM8-22 could attenuate bone cancer pain in mice. This study may provide a novel strategy for the treatment of bone cancer pain.
本研究旨在探究 Mas 相关 G 蛋白偶联受体 C(MrgC)激动剂牛肾上腺髓质 8 - 22(BAM8 - 22)对骨癌疼痛和镜像痛的影响。
通过向小鼠髓腔内注射 NC2472 纤维肉瘤细胞诱导骨癌疼痛。在诱导骨癌后第 14 天鞘内注射 BAM8 - 22 和/或抗 MrgC 抗体,并检测它们对疼痛行为的影响。通过自发举足次数和 paw withdrawal mechanical threshold(PWMT)测试评估疼痛行为。使用蛋白质免疫印迹分析和免疫荧光测定法检测 MrgC 的表达。
荷瘤小鼠出现骨癌疼痛和镜像痛增加,而假手术处理的小鼠未出现。BAM8 - 22 剂量依赖性地减轻小鼠骨癌疼痛,在给药后 2 小时效果最佳,抗 MrgC 抗体可逆转 BAM8 - 22 的作用。然而,鞘内注射 BAM8 - 22 不影响镜像痛。此外,BAM8 - 22 刺激脊髓背角 MrgC 的表达。
MrgC 激动剂 BAM8 - 22 可减轻小鼠骨癌疼痛。本研究可能为骨癌疼痛的治疗提供一种新策略。