Presentation Authors: Kenny Roman*, Christel Hall, Anthony Schaeffer, Praveen Thumbikat, Chicago, IL
Introduction: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a taxing disorder that is characterized by development of persistent pelvic pain in men of any age. Effective therapeutic treatments are scarce, due to a poorly defined etiology and pathogenesis of CP/CPPS. Although several studies suggest that the transient receptor potential vanilloid 1 (TRPV1) channel is involved in various pathways of chronic pain and a new generation of compounds that target the TRPV1 channel seem promising, the TRPV1 channel has not been linked to chronic pelvic pain in CP/CPPS.
Methods: Male C57BL/6J (B6) and TRPV1 knockout (TRPV1 KO) mice (5-7 weeks old) were used to induce experimental autoimmune prostatitis (EAP) and compared to respective control cohorts. The prostate lobes, dorsal root ganglia (DRG), and spinal cord were excised at day 20. The prostate lobes were assessed for inflammation, TRPV1 expression, and mast cell activity by blinded observers. The lumbosacral region of the DRG and spinal cord were measured for phosphorylation of ERK1/2 (p-ERK1/2). In addition, B6 mice with EAP received intraurethral administration of a TRPV1 antagonist at day 20 (repeated every two days) and we assessed the development of pain compared to control cohorts at days 20, 25, 30, and 35.
Results: Our data showed that B6 mice with EAP developed markedly enhanced pelvic tactile allodynia at days 7, 14, and 20. Surprisingly, the data revealed that TRPV1 KO mice with EAP do not develop pelvic tactile allodynia between days 7 to 20 and demonstrate a similar tactile response to respective controls. The dorsal and lateral prostate (DLP) lobes excised from B6 mice and TRPV1 K0 with EAP showed increased inflammation. Also, the DLP from B6 mice with EAP contained similar levels of TRPV1 compared to controls. In contrast, B6 mice with EAP showed a significant increase of mast cell activation. Interestingly, the DLP lobes from TRPV1 KO mice with EAP showed a lack of mast cell activation. Next, we observed a significant increase of p-ERK1/2 in the lumbosacral region of the DRG and spinal cord of B6 mice with EAP at day 20; however, p-ERK1/2 expression was unchanged in TRPV1 KO mice with EAP. In a separate experiment, we administered a TRPV1 antagonist peptide intraurethrally to the prostate and blunted the progression of pelvic tactile allodynia in mice with EAP.
Conclusions: The TRPV1 channel is a key mediator in persistent pelvic pain in EAP and intraurethral delivery of a TRPV1 antagonist peptide to the prostate may be a novel approach to alleviate chronic pelvic pain.
Source of Funding: This project was supported by award number F32 DK104544 (KR) and R01 DK083609 (PT) from the National Institute OfDiabetes And Digestive And Kidney Diseases.