The aim of this study is to elucidate the pathophysiological mechanisms of urethral instability. Within the existing literature, there has been an ongoing search for normal values and cut-off points, attempting to distinguish between what is considered within the realm of physiological variability and what should be considered as pathological instability. A better way to understand the phenomena of urethral instability would be to analyze the pattern and determine the underlying cause of the pressure variations.

Comparative analysis of urodynamic data derived from two female subjects, one exhibiting urethral instability with fast urethral pressure variations exceeding 30 cmH2O during bladder filling and the other without lower urinary tract dysfunction. These data were put against the backdground of existing literature. The study involved collecting data concerning urethral pressure at three distinct points within the urethra, coupled with continuous needle electromyography (EMG) measurements focusing on the external striated urethral sphincter (EUS). Bladder and abdominal pressure were recorded simultaneously throughout the procedure in accordance with established urodynamic guidelines. Additionally, a comprehensive literature review was conducted, focusing on the functional dynamics of various urethral muscle groups.

During normal micturition, urethral pressure gradually declines over a period of approximately 9 seconds after cessation of EMG activity of the external sphincter (figure 1). In contrast, in urethral instability, there is a rapid steep decrease in urethral pressure after a period of silence of the EMG signal of the striated external urethral muscle(ES) followed by a steep increase in urethral pressure with a concomitant burst of the EMG of the EUS (figure 2). The sudden urethral pressure decrease co-occurred with a subjective feeling of urgency to void. The urethral  instability started at the onset of bladder filling and exhibited a relatively high maximum urethral pressure of 85 cmH2O.

An additional review of the literature supported both our observations that the onset of urethral instability is already at the start of the bladder filling and supported the assumption that urethral pressure is determined by the activity of smooth urethral musculature. At the start of bladder filling, distension of the bladder produces a low-level vesical afferent firing, stimulating sympathetic outflow in the hypogastric nerve to the smooth urethral musculature to maintain continence.
Our findings suggest that in urethral instability,  the rapid decrease in urethral pressure following the cessation of EUS activity is due to a loss of urethral smooth muscle tone by an altered behavior of smooth urethral musculature at the start of bladder filling.
The sudden rise in urethral pressure is likely a guarding reflex effectuated by the EUS in response to fluid entering the urethra in an attempt to close the urethra and to prevent urine loss. 
From previous studies is also learned that in the bladder, the urothelium itself has neuron-like properties, contributing to sensory transduction mechanisms. Activation of adrenoceptor B3 (ADRB3) on urothelial cells triggers production and release of nitric oxide (NO). For the urethra, no similar findings have been reported,  presence of ADRB3 was demonstrated,  but with lack of contact between ADRB3 and neurons in the submucosal layer.  This could suggest the presence of an extra afferent signaling network originating from the urethral epithelial layer resulting in NO release as well when stimulated. Past studies suggested that alterations in NO-levels may play a role in urothelial signaling in the bladder. The female urethra has a rich vascular plexus and vascular smooth muscle cells are recognized as targets for NO. 
Previous research demonstrated that the enzyme cyclic nucleotide phosphodiesterase 5 (PDE5)  inhibitors promote potent relaxation of animal and human urethral smooth muscle.  Extrapolation of these data suggest that PDE5 inhibitors could have an effect on female urethral function as well, an interesting hypothesis for future research.

Urethral instability can be explained by contractions and relaxations of the EUS and are manifestations of a guarding reflex triggered by the loss of smooth urethral muscle function. This loss leads to impaired urethral closure, allowing fluid to enter the proximal urethra, resulting in the sense of urgency to void, followed by reflex contractions of the external sphincter to close the urethra. This may be due to high basal tension in urethral smooth muscles, causing them to relax early in response to low-level vesical afferent firing during the filling phase of the bladder.
Therapeutically, addressing urethral instability involves lowering basal urethral tension  to prevent relaxation of urethral smooth musculature during the storage phase of the bladder. Medical treatments with adrenergic beta-3 receptor agonists or alpha blockers have demonstrated efficacy in lowering urethral pressure and significantly reducing urethral pressure variations.  If a similar afferent signaling pathway, like in the bladder urothelium, also exists in the urethra, this could be of interest for future research to the role of pharmacotherapy in regard to urethral function