Interstitial Cystitis: Chronic Relief from Neuromodulation by Implantable Medical Device

An April 26, 2010 MedScape Today article by Jill Stein reported on a presentation of the results of a long term study of the effects of sacral neuromodulation on refractory painful bladder syndrome/interstitial cystitis (PBS/IC, Ref 1). The researchers reported durable effects with a median improvement in symptoms of 80% in 72% of patients (all who maintained the device) over a mean period of 61.5 months.

PBS/IC is a devastating disease characterized by pain in the bladder without any sign of infection. Patients with PBS/IC not only suffer pain, but also bladder capacities often so small as to be socially debilitating. Classical IC is characterized further by ulcerations in the mucosal lining of the bladder (Hunner’s ulcer), and may be a different disease than the non-ulcerative type (the distinction may reflect a similar set of differences, as seen in the gastrointestinal tract, between irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD)).

The ultimate causes of PBS/IC remain elusive, with disruptions of the barrier function of the urinary tract epithelial lining suspected as being key. However, the diagnosis of PBS/IC is made based on lack of evidence of any other disease state (such as infection, peripheral neuropathy, etc.), making PBS/IC a diagnosis of exclusion. So, what is the cause of PBS/IC? Historically, PBS/IC has been thought to be driven by prior peripheral insult, such that in susceptible individuals, a bladder infection or two results later in a lifetime of pain. Some believe that there is cross-sensitization of pelvic organs, such that a frank insult to the colon could result in PBS/IC by sensitizing afferents peripherally as well as by subsequent central sensitization mechanisms. In this way of thinking, PBS/IC is a “bottom-up” driven disease process.

More recently, the anecdotal observation that many patients with functional pain disorders, such as PBS/IC and irritable bowel syndrome (IBS), are hyper-vigilant and tend to suffer from anxiety disorders has been formalized by study. This, together with differences in regional brain responses to environmental stimuli, has led to the notion that the origin of chronic functional pain syndromes is tied more to the behavioral phenotype of the sufferer rather than by being driven from the periphery to the central nervous system. That is to say that whatever is responsible for the behavioral phenotype is also responsible for producing an inappropriate sensory experience in response to normal peripheral afferent input. Thus, proponents of this view are taking a “top-down” approach.

Sacral neuromodulation is achieved by direct electrical stimulation of sacral spinal roots in such a way as to modulate sensory input in the periphery prior to it entering the spinal cord. Thus, the recent report that sacral neuromodulation results in a long term amelioration of symptoms is important as it supports the historical “bottom-up” mechanism as a continued viable player. This is not to say that it is the only player – as with most things, the truth probably lies somewhere in between, with the behavioral phenotype influencing in a “top-down” fashion who develops PBS/IC from peripheral “bottom-up” stimuli.

Ref 1 – Abstract 646; J. Gajewski, A. Alzahrani, Sacral nerve root neuromodulation for the treatment of intractable painful bladder syndrome/interstitial cystitis (PBS/IC): 14 years experience of one center. Presented at the European Association of Urology (EAU) 25th Annual Congress on April 18, 2010.

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