4th International Consultation On Incontinence (ICI) - Neural Control Committee Highlights

Main Category: Urology / Nephrology
Article Date: 25 Jul 2008 - 1:00 PDT

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PARIS, FRANCE (UroToday.com) - The committee divided their presentation into two sections; the first on the "periphery" and the second part on "higher centers and pathophysiology."

Dr. Birder began by reviewing the neuroanatomy of the lower urinary tract and the barrier function of the urothelium. She described how surface vesicle fusion during urothelial stretch helps to maintain the barrier function (trafficking) and how this mechanism my also help regulate neurotransmiiter release and surface receptor composition. In addition to the well-known barrier function, Dr. Birder presented new findings that suggest that the urothelium plays a primary role as a transducer of physical and chemical stimuli. First, the urothelium expresses cell surface receptors (such as P2X) and ion channels (such as TRPV1) which are similar to those found on afferent nerves. In addition, the urothelium can release neurotransmitters, such as ATP) which can activate suburothelial afferent nerves in response to stretch or chemical stimuli.

Dr. Birder highlighted new findings regarding bladder afferent nerves, including a discussion of "silent" C-fibers which may only become active during inflammation. In additional, emotional stress has recently been shown to enhance mechanical hyperalgesia which may be due to activation of previously silent afferent mechanoreceptors. Dr. Birder suggested these alterations may play a role in Bladder Pain Syndrome.

Next, Dr. Birder described the chemical "cross-talk" between pelvic viscera and how disorders of one pelvic organ may influence not only other pelvic organs, but also the associated sphincters, pelvic floor musculature and abdominal wall. This may be due to convergence of afferent nerves at the dorsal root ganglia or higher centers. Finally, Dr. Birder noted that both neuronal and non-neuronal cells in the lower urinary tract exhibit plasticity in response to disease states and that some of these changes may be important in bladder/pelvic pain.

Dr. Birder then turned the presentation over to Dr. Marcus Drake (U.K.) who went on the describe the CNS hierarchy of the lower urinary and gastrointestinal tracts. Much of his presentation focused on findings from newer techniques such as functional MRI and PET scans. He cautioned that we do not necessarily know how to interpret findings on functional studies as they merely show areas of increased blood blow; the physiological implications remain unclear. He focused on several major areas including the periaqueductal gray (PAG) area which seems to monitor afferent activity and signal the pontine micturition center (PMC) to trigger to the voiding phase, and the L region of the PMC which is involved in maintaining continence.

Dr. Drake then outlined the new findings regarding cortical control and inhibition of the midbrain centers. The areas showing the highest activity on functional imaging seem to be the insular cortex, the prefrontal cortex and the anterior cingulated cortex. These areas appear to supply tonic inhibition to the PAG area until voiding is desired. Patients with detrusor overactivity have different patterns of activation on bladder filling.

Dr. Drake then discussed some work on the gastrointestinal tract which may have relevance to the lower urinary tract and chronic pain syndromes. He described the "Homeopathic Afferent Processing Network" which is responsible for processing visceral afferent inputs. Normally, we are not conscious of these stimuli but alterations in emotion or cognition may alter our awareness and we may become conscious of visceral stimuli. This was supported by an fMRI study of patients with inflammatory bowel syndrome who underwent rectal balloon distention. Subjects that were warned of impending distention had greater activation in the anterior insula both before and during distention when compared with subjects that were not warned.

Finally, Dr. Drake outlined the enteric nervous system and similarities with the bladder. There are intrinsic primary afferent neurons which can produce autonomous reflex activation. At small levels, this may not produce a pressure change on urodynamic study (sensory urge?) but larger areas of coordination may cause a detectable contraction (DO).

Lori Birder, MD, Committee Chair

Moderated by William C. de Groat, Ph.D., Professor, and L. Denis, MD, at the Fourth International Consultation on Incontinence (ICI) - July 5 - 8, 2008. Palais des Congres, Paris, France.

Written by William Jaffe, MD, a Contributing Editor with UroToday.

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