Activation of Transient Receptor Potential Vanilloid 1 Is Involved in Both Pain and Tumor Growth in a Mouse Model of Cancer Pain

Abstract

Activation of calcitonin gene-related peptide (CGRP)-positive sensory neurons in the tumor microenvironment has been shown to be involved in tumor growth. However, how CGRP-positive sensory neurons are activated requires elucidation. In this study, we focused on transient receptor potential vanilloid 1 (TRPV1) and examined the contribution of TRPV1 to tumor growth and cancer pain in a mouse cancer model in which Lewis lung carcinoma was subcutaneously inoculated in the left plantar region. Tumor inoculation gradually increased the volumes of the hind paws of wild type (WT) mice over time, but those of both αCGRP knockout mice and TRPV1 knockout mice were significantly smaller than those of WT mice after tumor inoculation. Both TRPV1 and CGRP are therefore suggested to be involved in tumor growth. In an immunohistochemical study, the percentage of phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB)-positive profiles in CGRP-positive dorsal root ganglion (DRG) neurons in WT mice was significantly increased after tumor inoculation. The percentage of p-CREB-positive profiles in CGRP-positive DRG neurons in TRPV1 knockout mice was also increased after tumor inoculation, but was significantly lower than that in WT mice, indicating the contribution of TRPV1 to activation of CGRP-positive DRG neurons. Cancer pain in TRPV1 knockout mice was significantly lower than that in WT mice. In conclusion, TRPV1 is involved in both tumor growth and cancer pain, potentially leading to a novel strategy for the treatment of cancer pain and cancer development. Cancer pain is also suggested to facilitate tumor growth.

Keywords: calcitonin gene-related peptide; dorsal root ganglion; hyperalgesia; pain; tumor growth.