Gabapentin, an Analgesic Used Against Cancer‐Associated Neuropathic Pain: Effects on Prostate Cancer Progression in anIn VivoRat Model

Abstract

A major problem associated with clinical management of cancer is controlling the accompanying pain, and various analgesics are in common use for this purpose. Recent evidence suggests that some of the targets of analgesics, such as ion channels and receptors, may also be involved in the cancer process, thereby raising the possibility that such use of some analgesics may impact upon cancer itself. The main aim of this study was to determine whether gabapentin, a common adjuvant analgesic in current use against cancer-associated neuropathic pain, would affect tumour development and progression in vivo. The Dunning rat model of prostate cancer was used. Strongly metastatic Mat-LyLu cells were implanted subcutaneously into syngeneic Copenhagen rats which were then treated every other day with 4.6-16.8 lg/kg gabapentin by gavage. Primary tumourigenesis was monitored daily. Lung metastases were counted and measured after killing the rats 21 days later. Gabapentin had no effect on primary tumourigenesis but produced dose-dependent effects on lung metastasis. Whilst 4.6 lg/kg had no effect, 9.1 lg/kg gabapentin decreased the number of lung metastases significantly by 64%. In contrast, 16.8 lg/kg gabapentin promoted metastasis significantly by 112% and showed a strong tendency to shorten mean survival time. It is concluded that gabapentin prescribed to cancer patients against pain could impact upon the cancer process itself.

Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

“…In vivo, local injection of the highly specific VGSC blocker, tetrodotoxin (TTX), into primary tumours significantly reduced metastases to lungs and prolonged survival 14 . In contrast, proliferative activity in vitro and in vivo was not affected by VGSC blockage consistent with the notion that primary tumorigenesis (ie proliferation) and metastasis (ie invasion) are controlled differently, even partially independently 15‐18 . Finally, quantitative analysis of “receiver operator characteristics” (ROC) in human biopsy tissues suggested that Nav1.7 mRNA expression had sufficient selectivity and specificity to serve as an effective biomarker of PCa 6 …”

Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

“…In vivo, local injection of the highly specific VGSC blocker, tetrodotoxin (TTX), into primary tumours significantly reduced metastases to lungs and prolonged survival 14 . In contrast, proliferative activity in vitro and in vivo was not affected by VGSC blockage consistent with the notion that primary tumorigenesis (ie proliferation) and metastasis (ie invasion) are controlled differently, even partially independently 15‐18 . Finally, quantitative analysis of “receiver operator characteristics” (ROC) in human biopsy tissues suggested that Nav1.7 mRNA expression had sufficient selectivity and specificity to serve as an effective biomarker of PCa 6 …”

Exposure to Psychotropic Drugs and Colorectal Cancer Risk in Patients with Affective Disorder: A Nested Case-Control Study

“…Although gabapentin is a well-known voltage-gated calcium channel inhibitor, it also presented a voltage-gated sodium channel blocking property 45 . It has been shown to suppress invasion and metastasis of prostate cancer cells in an animal model 46 . Lithium, another commonly used mood stabilizer with different mechanisms, has also been reported to be associated with a lower risk of overall cancer in epidemiology studies 3 47 .…”

A Meta-Analysis Showing the Quantitative Evidence Base of Preemptive Pregabalin for Postoperative Pain from Cancer-Related Surgery

“…Due to the lack of sufficient data, severe adverse reactions like delirium could not be assessed. Additionally, the gabapentin class of drugs, especially at higher doses, may affect the metastatic progression of tumor cells through disruption of Ca2 + signaling in Mat-LyLu cells in prostate cancer [ 52 , 53 ]. Even if the available data are largely controversial and inadequate at present, the use of pregabalin warrants caution [ 53 ].…”

Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

“…In vivo, local injection of the highly specific VGSC blocker, tetrodotoxin (TTX), into primary tumours significantly reduced metastases to lungs and prolonged survival 14 . In contrast, proliferative activity in vitro and in vivo was not affected by VGSC blockage consistent with the notion that primary tumorigenesis (ie proliferation) and metastasis (ie invasion) are controlled differently, even partially independently 15‐18 . Finally, quantitative analysis of “receiver operator characteristics” (ROC) in human biopsy tissues suggested that Nav1.7 mRNA expression had sufficient selectivity and specificity to serve as an effective biomarker of PCa 6 …”

Exposure to Psychotropic Drugs and Colorectal Cancer Risk in Patients with Affective Disorder: A Nested Case-Control Study

“…Although gabapentin is a well-known voltage-gated calcium channel inhibitor, it also presented a voltage-gated sodium channel blocking property 45 . It has been shown to suppress invasion and metastasis of prostate cancer cells in an animal model 46 . Lithium, another commonly used mood stabilizer with different mechanisms, has also been reported to be associated with a lower risk of overall cancer in epidemiology studies 3 47 .…”

A Meta-Analysis Showing the Quantitative Evidence Base of Preemptive Pregabalin for Postoperative Pain from Cancer-Related Surgery

“…Due to the lack of sufficient data, severe adverse reactions like delirium could not be assessed. Additionally, the gabapentin class of drugs, especially at higher doses, may affect the metastatic progression of tumor cells through disruption of Ca2 + signaling in Mat-LyLu cells in prostate cancer [ 52 , 53 ]. Even if the available data are largely controversial and inadequate at present, the use of pregabalin warrants caution [ 53 ].…”

Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

“…In vivo, local injection of the highly specific VGSC blocker, tetrodotoxin (TTX), into primary tumours significantly reduced metastases to lungs and prolonged survival 14 . In contrast, proliferative activity in vitro and in vivo was not affected by VGSC blockage consistent with the notion that primary tumorigenesis (ie proliferation) and metastasis (ie invasion) are controlled differently, even partially independently 15‐18 . Finally, quantitative analysis of “receiver operator characteristics” (ROC) in human biopsy tissues suggested that Nav1.7 mRNA expression had sufficient selectivity and specificity to serve as an effective biomarker of PCa 6 …”

Exposure to Psychotropic Drugs and Colorectal Cancer Risk in Patients with Affective Disorder: A Nested Case-Control Study

“…Although gabapentin is a well-known voltage-gated calcium channel inhibitor, it also presented a voltage-gated sodium channel blocking property 45 . It has been shown to suppress invasion and metastasis of prostate cancer cells in an animal model 46 . Lithium, another commonly used mood stabilizer with different mechanisms, has also been reported to be associated with a lower risk of overall cancer in epidemiology studies 3 47 .…”

A Meta-Analysis Showing the Quantitative Evidence Base of Preemptive Pregabalin for Postoperative Pain from Cancer-Related Surgery

“…Due to the lack of sufficient data, severe adverse reactions like delirium could not be assessed. Additionally, the gabapentin class of drugs, especially at higher doses, may affect the metastatic progression of tumor cells through disruption of Ca2 + signaling in Mat-LyLu cells in prostate cancer [ 52 , 53 ]. Even if the available data are largely controversial and inadequate at present, the use of pregabalin warrants caution [ 53 ].…”