Functional constipation induces bladder overactivity associated with upregulations of Htr2 and Trpv2 pathways

Area of Science:

• Pediatric Urology
• Gastroenterology
• Neuroscience

Background:

• Bladder and bowel dysfunction (BBD) is a common pediatric condition involving lower urinary tract symptoms (LUTS) and bowel issues like constipation.
• BBD is a risk factor for long-term urinary tract problems, but its underlying mechanisms and treatments are not well understood.

Purpose of the Study:

• To investigate the impact of constipation on lower urinary tract function in a juvenile animal model.
• To explore the role of serotonin receptors in constipation-induced bladder changes.

Main Methods:

• A juvenile murine model was used to induce functional constipation for four days.
• Awake cystometry evaluated LUTS, and in vitro bladder strip physiology assessed detrusor function.
• Serotonin receptor expression (Htr2a, Htr2c) and response to serotonin were analyzed.

Main Results:

• Constipation led to LUTS, including urinary frequency and detrusor overactivity.
• Bladder strips showed increased spontaneous contractions, with enhanced response to serotonin.
• Serotonin receptors Htr2a and Htr2c were upregulated in bladders of constipated mice.

Conclusions:

• Constipation induces detrusor overactivity in juvenile mice.
• Increased excitatory serotonin receptor activation in the bladder contributes to BBD development.
• Findings suggest a link between constipation, serotonin signaling, and pediatric bladder dysfunction.