Role of TRPV1 channels in mediating chronic pelvic pain and the role of inflammation in prostate cancer

Author/Creator

Author/Creator ORCID

Date

2017-01-01

Type of Work

Department

Biological Sciences

Program

Biological Sciences

Citation of Original Publication

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Abstract

Chronic Prostatitis/ Chronic Pelvic Pain Syndrome (CP/CPPS) forms around 90% of the 2 million prostatitis cases. CP/CPPS is accompanied by excruciating pelvic pain for which the etiology is unknown. Current analgesics include tricyclic antidepressants and anti-convulsants that have a plethora of side effects. Identification of the etiology of chronic pelvic pain is instrumental for the development of better therapies. Transient Receptor Potential (TRP) channels have been shown previously to play an important role in mediating pain responses. TRPV1 channels are vanniloid receptors that are known to play a role in inflammatory pain. In this study we show the role of TRPV1 channels in mediating chronic pelvic pain in our mouse model of IL-1? mediated prostate inflammation. ABT-102 is a selective TRPV1 antagonist that has been shown to alleviate pain in murine models of bone cancer and post-operative pain. In addition, we show that blocking these TRPV1 channels with ABT-102 successfully and reversibly blocks pain sensation in our mouse model. Chronic prostatitis has also been linked to an increased risk of prostate cancer. Phosphatase tensin homolog (PTEN) is a tumor suppressor that is the most commonly mutated gene in prostate cancer. We have developed a mouse model by crossing our IMPI model with the Cre/PTENfl/fl model to generate mice with IMPI/Cre/PTEN. We show that upon induction of prostate inflammation combined with loss of one allele of PTEN using doxycycline we see infiltration by immune cells but no cellular atypia at 15 weeks. We also show that long term chronic inflammation in the IMPI model leads to the development of prostatic intraepithelial neoplasia (PIN) with a high penetrance. Using these results we further show the link between chronic inflammation and incidence of neoplastic lesions in the prostate.