Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas 1020A, Venezuela.
Laboratorio de Fisiología Celular, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas 1020A, Venezuela.
Int J Mol Sci. 2021 Sep 7;22(18):9671. doi: 10.3390/ijms22189671.
Cancer pain may be the consequence of physical nerve compression by a growing tumor. We employed a murine model to study whether gabapentin was able to regulate tumor growth, in addition to controlling hyperalgesic symptoms. A fluorescent melanoma cell line (B16-BL6/Zs green) was inoculated into the proximity of the sciatic nerve in male C57BL/6 mice. The tumor gradually compressed the nerve, causing hypersensitivity. Tumor growth was characterized via in vivo imaging techniques. Every other day, gabapentin (100 mg/Kg) or saline was IP administered to each animal. In the therapeutic protocol, gabapentin was administered once the tumor had induced increased nociception. In the preventive protocol, gabapentin was administered before the appearance of the positive signs. Additionally, in vitro experiments were performed to determine gabapentin's effects on cell-line proliferation, the secretion of the chemokine CCL2, and calcium influx. In the therapeutically treated animals, baseline responses to noxious stimuli were recovered, and tumors were significantly reduced. Similarly, gabapentin reduced tumor growth during the preventive treatment, but a relapse was noticed when the administration stopped. Gabapentin also inhibited cell proliferation, the secretion of CCL2, and calcium influx. These results suggest that gabapentin might represent a multivalent strategy to control cancer-associated events in painful tumors.
癌症疼痛可能是由于生长的肿瘤对神经的物理性压迫所致。我们采用了一种小鼠模型来研究加巴喷丁是否除了控制痛觉过敏症状外,还能够调节肿瘤生长。将荧光黑素瘤细胞系(B16-BL6/Zs 绿色)接种到雄性 C57BL/6 小鼠坐骨神经附近。肿瘤逐渐压迫神经,导致感觉过敏。通过体内成像技术来描述肿瘤生长。每隔一天,向每只动物腹腔内注射 100mg/Kg 的加巴喷丁或生理盐水。在治疗方案中,当肿瘤引起痛觉过敏增加时,给予加巴喷丁。在预防方案中,在出现阳性迹象之前给予加巴喷丁。此外,还进行了体外实验来确定加巴喷丁对细胞系增殖、趋化因子 CCL2 的分泌和钙内流的影响。在接受治疗的动物中,对有害刺激的基线反应得到恢复,并且肿瘤明显缩小。同样,加巴喷丁在预防性治疗中也减少了肿瘤生长,但当停止给药时,出现了复发。加巴喷丁还抑制了细胞增殖、CCL2 的分泌和钙内流。这些结果表明,加巴喷丁可能代表一种多效策略,可用于控制疼痛性肿瘤中的癌症相关事件。