Chen Yunlong, Wu Mianhua
Department of Oncology, Rudong County Hospital of Traditional Chinese Medicine, Rudong County 226400, Jiangsu, China.
Institute of Oncology, The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China.
Aging (Albany NY). 2024 Nov 19;16(21):13288-13303. doi: 10.18632/aging.205908.
Severe painful neuropathy often occurs in cancer patients receiving chemotherapy. Emerging evidence has demonstrated that microglia contribute to the occurrence and development of cancer-associated pain. This study aimed to investigate the mechanisms by which piperine influences cancer-associated pain induced by microglia activation.
The tumor cell implantation (TCI) model was adopted as the cancer-associated pain model in mice. Behavioral tests were done to confirm that model mice were sensitive to acute mechanical and thermal pain. Western blot (WB) and immunofluorescence (IF) were conducted to quantify expression level of microglia marker protein Iba1 in mice spinal cord tissues. The expression of miR-150-5p and CXCL12 in the mice spinal cord was evaluated by Quantitative real-time Polymerase Chain Reaction (qRT-PCR) and fluorescence hybridization (FISH). Primary microglia from mice were treated with lipopolysaccharide (LPS) to investigate neuroinflammation.
The modeled mice showed high susceptibility to acute mechanical hyperalgesia and thermal hyperalgesia. The expression of microglia marker protein Iba1 in the model group was increased and . Treatment with piperine effectively relieved the cancer-associated pain in mice. The results of FISH and qRT-PCR showed that piperine significantly increased the expression of miR-150-5p and reduced the expression of CXCL12 in the spinal cord of mice. Furthermore, it inhibited the microglia-induced cancer-associated pain.
Piperine upregulates miR-150-50p levels, inhibits CXCL12 expression, and reduces microglia levels at the lesion site. Therefore, piperine may be a potential drug candidate for the treatment of cancer-associated pain.
严重疼痛性神经病变常发生于接受化疗的癌症患者中。新出现的证据表明，小胶质细胞促成了癌症相关性疼痛的发生和发展。本研究旨在探究胡椒碱影响小胶质细胞激活诱导的癌症相关性疼痛的机制。
采用肿瘤细胞植入（TCI）模型作为小鼠癌症相关性疼痛模型。进行行为测试以确认模型小鼠对急性机械性和热性疼痛敏感。采用蛋白质免疫印迹法（WB）和免疫荧光法（IF）对小鼠脊髓组织中小胶质细胞标志物蛋白Iba1的表达水平进行定量分析。通过定量实时聚合酶链反应（qRT-PCR）和荧光杂交（FISH）评估小鼠脊髓中miR-150-5p和CXCL12的表达。用脂多糖（LPS）处理小鼠原代小胶质细胞以研究神经炎症。
模型小鼠对急性机械性痛觉过敏和热性痛觉过敏表现出高敏感性。模型组中小胶质细胞标志物蛋白Iba1的表达增加。胡椒碱治疗有效缓解了小鼠的癌症相关性疼痛。FISH和qRT-PCR结果显示，胡椒碱显著增加了小鼠脊髓中miR-150-5p的表达并降低了CXCL12的表达。此外，它抑制了小胶质细胞诱导的癌症相关性疼痛。
胡椒碱上调miR-150-50p水平，抑制CXCL12表达，并降低损伤部位的小胶质细胞水平。因此，胡椒碱可能是治疗癌症相关性疼痛的潜在候选药物。
