The role of TRPV1 in chronic prostatitis: a review

Abstract

Chronic prostatitis is a prevalent male urinary system disorder characterized by pelvic discomfort or pain, bladder dysfunction, sexual dysfunction, and infertility. Pain and lower urinary tract symptoms (LUTS) are the most common symptoms, significantly impacting patients' quality of life and driving them to seek medical attention. Transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective calcium ion-dependent cation channel in the TRPV channel family that is widely distributed in neural tissue and plays a role in signal transmission. In this review, we provide a comprehensive overview of the current understanding of the role of TRPV1 in chronic prostatitis. The discussion focuses on the connection between TRPV1 and prostatitis pain and LUTS, and highlights the potential for targeting this channel in the development of novel treatment strategies.

Keywords: TRPV1 channel; lower urinary tract symptoms; pain; prostatitis; therapeutic target.

FIGURE 1

The structure of TRPV1 channel protein. It consists of a tetramer, with each subunit comprising 6 transmembrane domains (S1-S6) on the cell membrane, along with the N-terminus and C-terminus within the cell. The hydrophobic group formed by the transmembrane domains forms a pore that allows cations to pass through. The N-terminal serves as a site for phosphorylation and ankyrin binding, while the C-terminal acts as a binding site for endogenous substances and calcium ions. CAP binding sites are Tyr511, Ser512, and Thr550; RTX binding sites are Leu515, Phe543, Asn551, and Tyr555; Heat-sensitive binding sites are 686–741, 751–838, and F640L. Abbreviations: TRPV1, transient receptor potential vanilloid subtype 1; CAP, Capsaicin; RTX, Resiniferatoxin. Image was created with BioRender.com.

FIGURE 2

Briefly explain the mechanism of CP/CPPS pain and lower urinary tract. The accumulation of inflammatory factors in the prostate, along with the activation and degranulation of mast cells, results in the sensitization of C-fibers nerve endings in the prostate. This sensitization causes the DRG neurons, which innervate both the prostate and bladder, to express elevated levels of SP, CGRP, and NGF. The release of these neuropeptides into the central nervous system contributes to pain sensitization. Additionally, a significant number of antidromic nerve impulses are generated through dorsal root reflexes or local axonal reflexes, which further release these substances peripherally, leading to a neurogenic inflammatory response in the prostate or bladder. This response can exacerbate pain sensitization or may also contribute to bladder dysfunction. Furthermore, NGF influences sensory nerve endings in the prostate or bladder and can be transported from the periphery to DRG neurons. Upon binding to Trk, NGF enhances neuronal excitability, thereby further sensitizing pain. Green arrows represent the effects of different substances on sensory nerves or receptors; brown arrows represent the transport direction of SP, CGRP and NGF; light red dotted arrows represent the direction of nerve impulse transmission. Abbreviations: TNF-α, tumor necrosis factor-alpha; IL-8, interleukin-8; IFN-γ,interferon-gamma; IL-4, interleukin-4; IL-6, interleukin-6; IL-10, interleukin-10; NGF, nerve growth factor; CGRG, calcitonin gene peptide; SP, substance P; DRG, dorsal root ganglion; Trk, tropomyosin receptor kinase; TRPV1, transient receptor potential vanilloid subtype 1; DRG, dorsal root ganglia; C-fiber, capsaicin-sensitive afferent fiber. Image was created with BioRender.com.