Bladder outlet obstruction (BOO) could be caused by anatomical (eg. benign prostatic obstruction, BPO) or functional (eg. bladder neck dysfunction, BND) etiologies. The dysfunction of urethra might play an important role in the pathophysiology of BOO. This study investigated the sensory proteins in urethral mucosa between BPO and BND.

We prospectively investigated urethra mucosal tissue obtained from the operations of transurethral incision and resection in 32 BND and 27 BPO patients, respectively. The specimen was divided into bladder neck (BN) and prostatic urethra two parts for comparison. The expressions of α1A and β3 adrenoreceptor, M2 and M3 muscarinic receptors, TGF-β, and TRPV1 by Western blotting were compared between BPO and BND patients. In BND patients, urethral sensory protein expressions and autonomic nervous system (ANS) function evaluated with heart rate variability (HRV) were also compared between surgical success and failure groups.

BPO patients had higher expression of α1A adrenoreceptor in BN but lower expression of M2 muscarinic receptor in prostatic urethra than BND patients (Table 1). In BND patients, success group had higher expressions of α1A adrenoreceptor and TRPV1 in both BN and prostatic urethra, higher expression of M3 muscarinic receptor in BN, and a higher LF/ HF (low frequency power/ high frequency power) ratio in HRV than failure group (Table 2). A positive correlation was noted between the expression of β3 adrenoreceptor in BN and HF power in HRV (r=0.570), and also between the expression of TGF-β in BN and LF/ HF ratio in HRV (r=0.525).

BPO and BND patients had different sensory protein expressions in urethra mucosa, indicating their different pathophysiology. The operation of transurethral incision of BN damaged the integrity of BN, which was innervated by sympathetic nerves. In success group of BND patients, higher expressions of α1A adrenoreceptor in BN and prostatic urethra were detected in addition to the higher LF/ HF ratio, all of which indicated the predominant sympathetic nerve activities. It suggested that BND patients with predominant sympathetic nerve activities might have better surgical outcomes. In contrary, BND patients without predominant sympathetic nerve activities had poor surgical outcomes, and the detrusor contractility and the function of external urethral sphincter might involve to complicate the pathomechanism. The correlation between the regional expressions of urethra sensory proteins and the systemic ANS function by HRV parameters was also detected. It indicated the connection between regional and systematic ANS functions, both of which play important roles in the pathophysiology of BND.

BPO and BND patients had different sensory protein expressions in urethra mucosa, indicating their different pathophysiology. In BND patients, urethral mucosal dysfunction with distinct sensory protein expressions and ANS dysfunction might play important roles in the treatment outcome and reflex the complex pathophysiology