Concomitant Antihyperalgesic and Antitumor Effects of Gabapentin in a Murine Cancer Pain Model

Abstract

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.