Enhancement sensitivity of TRPV1 in dorsal root ganglia via the SP-NK-1 pathway contributes to increased bladder organ sensitivity caused by prostatitis

Abstract

Chronic prostatitis/chronic pelvic pain syndrome is a prevalent condition affecting the male urinary system. The urinary dysfunction resulting from this disorder has a direct or indirect impact on the patient's quality of life. Recent studies have suggested that organ cross-sensitization between the prostate and bladder may elucidate this phenomenon; however, the specific molecular mechanisms remain unclear. In this study, we simulated the urinary symptoms of prostatitis patients using an animal model and examined the expression of relevant proteins within the prostate-bladder sensitized neural pathway. We found that transient receptor potential vanilloid 1 (TRPV1) protein is highly expressed in the dorsal root ganglia (DRG) that co-innervate both the prostate and bladder, potentially increasing the sensitivity of TRPV1 channels via the substance P-neurokinin 1 (SP-NK-1) pathway, which may exacerbate micturition symptoms. Furthermore, in the absence of bladder inflammation, elevated levels of neurogenic substances in bladder tissue were found to sensitize bladder sensory afferents. Collectively, these results underscore the significant role of TRPV1 in bladder sensitization associated with prostatitis, suggesting that the inhibition of TRPV1 along this sensitization pathway could be a promising approach to treating urinary dysfunction linked to prostatitis in the future.

Keywords: SP-NK-1 pathway; cross-organ sensitization; prostatitis; transient receptor potential vanilloid 1; urination disorder.

FIGURE 1

Urination behavior of rats with prostatitis. (A) The volume-to-area standard curve with formula. (B) Total urine output in 4 h. (C) Quantification of the number of micturition spots. (D) Average single urine output. Differences between groups were compared by an unpaired t-test. Data are expressed as mean ± SEM. *Significant difference compared with the Control group, *p < 0.05; “ns” indicates p > 0.05.

FIGURE 2

Establishment of the rat model of prostatic inflammation. (A,B) General view of prostate tissue and bladder tissue in each group; (C,D) HE staining of prostate tissue and bladder tissue in each group (magnification 100 × ); Scale bar, 100 × magnification is 100 um.

FIGURE 3

Expression of TRPV1, SP, and NK-1 in DRG. (A) Western blotting analysis results show increased expression of TRPV1, SP, and NK-1 in DRG in the prostatitis group. (B) The difference is statistically significant compared to the control group. ***p < 0.001 versus the control group. Data represents the mean ± SEM.

FIGURE 4

Expression of TRPV1 and SP in bladder. (A) Western blotting analysis results show increased expression of TRPV1 and SP in bladder in the prostatitis group. (B) The difference is statistically significant compared to the control group. *p < 0.05 versus the control group ****p < 0.0001 versus the control group. Data represents the mean ± SEM.

FIGURE 5

Immunofluorescence staining of transient receptor potential vanilloid 1 (TRPV1; green) and substance P (SP; red) in rat bladder tissue. TRPV1 and SP are predominantly expressed in the bladder urothelium, with a minor expression noted in the bladder muscle layer. Strong expression of both TRPV1 and SP was observed in the bladder urothelium of the prostatitis group. Co-localization analysis indicated that TRPV1 and SP are primarily distributed within the bladder urothelium. Scale bar, 40 × magnification is 200 um; Scale bar, 200 × magnification is 50 um.