The concept of peripheral modulation of bladder sensation

Abstract

It is recognized that, as the bladder fills, there is a corresponding increase in sensation. This awareness of the volume in the bladder is then used in a complex decision making process to determine if there is a need to void. It is also part of everyday experience that, when the bladder is full and sensations strong, these sensations can be suppressed and the desire to void postponed. The obvious explanation for such altered perceptions is that they occur centrally. However, this may not be the only mechanism. There are data to suggest that descending neural influences and local factors might regulate the sensitivity of the systems within the bladder wall generating afferent activity. Specifically, evidence is accumulating to suggest that the motor-sensory system within the bladder wall is influenced in this way. The motor-sensory system, first described over 100 years ago, appears to be a key component in the afferent outflow, the afferent “noise,” generated within the bladder wall. However, the presence and possible importance of this complex system in the generation of bladder sensation has been overlooked in recent years. As the bladder fills the motor activity increases, driven by cholinergic inputs and modulated, possibly, by sympathetic inputs. In this way information on bladder volume can be transmitted to the CNS. It can be argued that the ability to alter the sensitivity of the mechanisms generating the motor component of this motor-sensory system represents a possible indirect way to influence afferent activity and so the perception of bladder volume centrally. Furthermore, it is emerging that the apparent modulation of sensation by drugs to alleviate the symptoms of overactive bladder (OAB), the anti-cholinergics and the new generation of drugs the β3 sympathomimetics, may be the result of their ability to modulate the motor component of the motor sensory system. The possibility of controlling sensation, physiologically and pharmacologically, by influencing afferent firing at its point of origin is a “new” concept in bladder physiology. It is one that deserves careful consideration as it might have wider implications for our understanding of bladder pathology and in the development of new therapeutic drugs. In this overview, evidence for the concept peripheral modulation of bladder afferent outflow is explored.

Bladder telemetry: A new approach to evaluate micturition behavior under physiological and inflammatory conditions

“…With our model, the bladder reflex was not stimulated by an artificial mechanical filling but by a more physiological one via the kidneys. This suggests that when an animal decided to void, it was not only based on the volume but mostly on bladder sensation confirming a modification of the bladder sensation related to function in rat interstitial cystitis elicited by CYP.…”

Validation of a real‐time bladder sensation meter during oral hydration in healthy adults: Repeatability and effects of fill rate and ultrasound probe pressure

“…In addition, a second fill–void cycle may have more constant fill rates as the speed of bladder filling increases . With a constant fill rate, an individual's “awareness” during filling also increases, which may decrease variation in bladder sensations . Previous studies have suggested there is some “learning” effect as participants consciously evaluate their bladder sensations, further contributing to awareness and perceived sensations …”

The actions of isoprenaline and mirabegron in the isolated whole rat and guinea pig bladder

“…Interstitial cells were found to be excitable and able to transmit their electrical activity to the detrusor cells via gap junctions to generate propagating waves of contraction in the bladder wall Gray et al, 2013;Hashitani et al, 2004). It has been speculated that such an agonist stimulated, phasic and coordinated phenomenon of contractions may be related to the NVA seen during cystometric studies in conscious animals (Gillespie et al, 2012) and might be involved in the generation of bladder sensations (Eastham and Gillespie, 2013;Gillespie, 2004).…”

“…Horizontal dotted line: intrinsic baseline pressure before arecaidine administration. regulation of bladder contractile events (Eastham and Gillespie, 2013;Eastham et al, 2015). However, functional evidence for the role of the pelvic ganglia in the regulation of contractile activity and site of action of mirabegron remains to be established.…”

“…In addition, other targets have been suggested that include the urothelium (Kullmann et al, 2011;Masunaga et al, 2010) or pelvic ganglia (Eastham et al, 2015). However, with these additional speculative mechanisms the precise nature of the adrenergic component of the overall physiological system remains to be fully characterized (see Eastham and Gillespie, 2013 for an overview).…”