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

Beatriz Elena Brito,Leslie Baute,Geraldinee Bernal,Yetsenia María De Gouveia,Gabriel Díaz-Serrano,Pura Bolaños,Sindy Devis,Víctor Alejandro Tortorici-Brito,María Alejandra García,Víctor Tortorici

doi:10.3390/ijms22189671

Beatriz Elena Brito, Leslie Baute + Show 8 more

Open Access

https://doi.org/10.3390/ijms22189671

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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.

Highlights

Cancer is often a painful disease that affects the quality of life
Cancer-induced pain involves multiple symptoms such as hyperalgesia, allodynia, spontaneous pain, and numbness, which may be the consequence of physical nerve compression by the growing tumor, or direct infiltration of the nerve [2]; they may result from tissue acidosis, the release of chemical algogens by the tumor, or the effects of cancer-prescribed therapies [2]
The response was stable from that moment, reaching 1.66 ± 0.28 g and 3.32 ± 0.24 s at the end of the experiment

Summary

Introduction

Cancer is often a painful disease that affects the quality of life. At least 15–20% of patients are likely to suffer from pain during the course of the disease, and an even higher proportion of the population becomes affected at its advanced stages [1,2]. Various cancer-induced pain models involving the inoculation of murine tumor cells into the hind paw or the thigh of mice have been developed [3,4,5,6]. Inoculation readily induced heat hyperalgesia and mechanical allodynia. These symptoms reached a maximum around two weeks later, at a time when signs of nerve compromise could be identified [3,4,5,6]

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