Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Dec 1;315(6):F1583-F1591.
doi: 10.1152/ajprenal.00231.2018. Epub 2018 Aug 8.

Development of Stress-Induced Bladder Insufficiency Requires Functional TRPV1 Channels

Affiliations
Free PMC article

Development of Stress-Induced Bladder Insufficiency Requires Functional TRPV1 Channels

Nathan R Tykocki et al. Am J Physiol Renal Physiol. .
Free PMC article

Abstract

Social stress causes profound urinary bladder dysfunction in children that often continues into adulthood. We previously discovered that the intensity and duration of social stress influences whether bladder dysfunction presents as overactivity or underactivity. The transient receptor potential vanilloid type 1 (TRPV1) channel is integral in causing stress-induced bladder overactivity by increasing bladder sensory outflow, but little is known about the development of stress-induced bladder underactivity. We sought to determine if TRPV1 channels are involved in bladder underactivity caused by stress. Voiding function, sensory nerve activity, and bladder wall remodeling were assessed in C57BL/6 and TRPV1 knockout mice exposed to intensified social stress using conscious cystometry, ex vivo afferent nerve recordings, and histology. Intensified social stress increased void volume, intermicturition interval, bladder volume, and bladder wall collagen content in C57BL/6 mice, indicative of bladder wall remodeling and underactive bladder. However, afferent nerve activity was unchanged and unaffected by the TRPV1 antagonist capsazepine. Interestingly, all indices of bladder function were unchanged in TRPV1 knockout mice in response to social stress, even though corticotrophin-releasing hormone expression in Barrington's Nucleus still increased. These results suggest that TRPV1 channels in the periphery are a linchpin in the development of stress-induced bladder dysfunction, both with regard to increased sensory outflow that leads to overactive bladder and bladder wall decompensation that leads to underactive bladder. TRPV1 channels represent an intriguing target to prevent the development of stress-induced bladder dysfunction in children.

Keywords: TRPV1 channels; social stress; urinary bladder; voiding dysfunction.

Figures

Fig. 1.
Fig. 1.
Intensified social stress causes bladder underactivity in C57BL/6 mice. A and B: cystometric recordings from unstressed or stressed C57BL/6 mice, respectively. C and D: summary bar graphs showing that intensified social stress significantly increased intermicturition interval and void volume, respectively. *P ≤ 0.05; n = 5–6 mice.
Fig. 2.
Fig. 2.
Afferent nerve activity is unchanged by intensified social stress. Representative traces of intravesical pressure (top) and afferent nerve activity (bottom) from unstressed (A) or stressed mice (B). Summary graph (C) showing that intensified social stress had no effect on bladder afferent activity. Transient receptor potential vanilloid type 1 channel antagonist capsazepine (1–10 µM) (D) also had no effect on bladder afferent nerve activity in intensified stress mice. n = 6–10 mice.
Fig. 3.
Fig. 3.
Ex vivo bladder capacity and collagen deposition are increased in intensified stress mice. Bar graph (A) showing ex vivo bladder capacity (at 25 mmHg) in unstressed and intensified stress mice. Summary graph (B) and representative images of Masson trichrome staining of bladder sections from unstressed (C) and intensified stress (D) mice, showing increased collagen deposition (blue; white arrow) and a decrease in smooth muscle (red; black arrow). Representative of samples from 6 mice. Scale bar = 200 µm. *P ≤ 0.05; n = 5 mice. L, bladder lumen.
Fig. 4.
Fig. 4.
Intensified social stress does not affect bladder function in transient receptor potential vanilloid type 1 (TRPV1) knockout (KO) mice. Cystometric recordings from unstressed (A) or stressed (B) TRPV1-KO mice. Summary bar graphs (C) showing that neither mild nor intensified social stress affects intermicturition interval and void volume in TRPV1-KO mice. * P ≤ 0.05; n = 4–6 mice.
Fig. 5.
Fig. 5.
Ex vivo bladder capacity is unaltered in transient receptor potential vanilloid type 1 (TRPV1) knockout (KO) mice after intensified stress mice. Representative pressure-volume traces (A) and summary bar graph (B) showing ex vivo bladder capacity (at 25 mmHg) in unstressed C57BL/6 mice, intensified stress C57BL/6 mice, and intensified stress TRPV1-KO. *P ≤ 0.05; n = 5.
Fig. 6.
Fig. 6.
Collagen deposition are unaltered in transient receptor potential vanilloid type 1 (TRPV1) knockout (KO) mice after intensified stress mice. Masson trichrome staining of bladder sections from unstressed TRPV1-KO (A) and intensified stress TRPV1-KO (B) mice showing collagen deposition (blue; white arrow) and smooth muscle (red, black arrow). Intensified social stress (C) did not alter urinary bladder collagen expression in TRPV1-KO mice. Representative of samples from 5 mice. Scale bar = 200 µm. *P ≤ 0.05; n = 5. L, bladder lumen.
Fig. 7.
Fig. 7.
Intensified stress increases corticotropin-releasing hormone (CRH) mRNA expression in Barrington’s Nucleus (BN) from transient receptor potential vanilloid type 1 (TRPV1) knockout (KO) mice. Fluorescent in situ hybridization showing CRH-positive cells (green) in brain sections of Barrington’s Nucleus from unstressed (A) and intensified stress (B) TRPV1-KO mice. Summary bar graph (C) showing a significant increase in CRH-expressing cells in response to intensified social stress. *P ≤ 0.05; n = 4.

Similar articles

See all similar articles

Cited by 1 article

Publication types

MeSH terms

Substances

LinkOut - more resources

Feedback