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Cystitis
Lidocaine pain demonstrate efficacy of probiotic approaches (reviewed in
To gain temporary relief from the pain of IC, some patients seek reference 31). IBS is a chronic condition that shares striking
intravesical lidocaine therapy, either in the clinic or by self- similarities with IC, including unknown aetiology, regional pain,
administration.
23,24
While effective for symptoms, this strategy is exacerbation by comestibles and stress, mechanical organ
inconvenient. We found that colonic lidocaine significantly reduced dysfunction and postulated neuro-immune interactions mediated by
bladder-associated pelvic pain in mice, suggesting that a similar mast cells in the general absence of overt inflammation. IBS probiotic
strategy may prove useful in IC patients.
13
This possibility is also studies show that the various symptoms of IBS exhibit differential
consistent with observations that rectal lidocaine provides pain relief responses to probiotic formulations and treatment regimens. This
for IBS patients.
8,9
Rectal administration is less unpleasant than suggests that gut probiotics will require optimisation to reduce IC
transurethral administration and offers the additional advantage of pelvic pain through diminished spatial summation. Nonetheless, the
facilitating the use of non-liquid mediation, such as gels or IC/IBS similarities and the influence of the gut on bladder-associated
suppositories that would be retained longer in the rectum or colon. pelvic pain strongly warrant evaluating gut probiotics as a novel IC
Rectal anaesthetics for IC pain relief could also be combined with therapy based on organ cross-talk.
emerging strategies for enhancing anaesthetic efficacy. For example,
recent studies have demonstrated that the membrane-impermeant Conclusions
lidocaine derivative QX-314 can be specifically targeted to sensory Comestibles are now widely accepted as aggravating the symptoms
nerves when co-administered with capsacian.
25
In rat models, QX-314 of IC. This effect is likely mediated by organ cross-talk between the
provided more durable analgesia than lidocaine in response to bladder and the GI tract through neural integration and the process of
noxious mechanical and thermal stimuli yet produced none of the spatial summation. Since the gut can both positively and negatively
motor and tactile deficits associated with lidocaine. Thus, rectal modulate bladder-associated pain, dietary restriction may reduce IC
QX-314 may offer convenient, durable and specific relief for IC pelvic symptoms by eliminating a significant input in spatial summation. This
pain by acting through organ cross-talk. phenomenon may be exploited by adapting the current clinical use of
intravesical lidocaine for IC pain relief to colonic lidocaine, a more
Gut Microbiome and Probiotics for Interstitial Cystitis desirable modality for self-administration. Finally, the emerging
The human GI tract contains a large load of commensal bacteria – understanding of gut microbial ecology points to the potential for
approximately 10
12
organisms/ml – and it is increasingly appreciated developing novel IC pain approaches that target bladder–bowel
that the GI microbial flora can mediate disease pathogenesis. In cross-talk through gut probiotics. n
humans, characterisation of the GI microbiome by sequencing
bacterial 16S ribosomal RNA genes revealed that obesity is associated
David J Klumpp is an Associate Professor of Urology and
with altered relative abundance of Bacteroidetes and Firmicutes.
26
Microbiology-Immunology at Feinberg School of Medicine,
Recent studies utilising germ-free mice demonstrated that colonising Northwestern University in Chicago. He is also Co-Director
mice with an obese microbiota conferred an obese phenotype relative
of the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK)-sponsored Northwestern Center
to colonising mice with a lean microbiota.
27
A western diet was also
with the Multi-Disciplinary Approaches to Chronic Pelvic
found to induce skewing of the microbial flora towards a microbiome Pain (MAPP) Network. His research interests include
that enhanced fat deposition; these effects were reversible.
27,28 mechanisms of pelvic pain, pathogenesis of urinary tract
infections and inflammatory responses in the urinary
Consistent with these findings in mice, 16S analyses of obese and lean
tract. Dr Klumpp is Treasurer of the American Urological Association (AUA) Society for
twins in humans demonstrated that obesity is associated with a loss of Infection and Inflammation in Urology. He received his PhD in biochemistry, molecular
microbial diversity and phylum-level microbiota changes.
29
However,
biology and cell biology from Northwestern University in 1994.
the impact of the gut microbiome likely extends beyond calorie
Charles N Rudick is a Research Assistant Professor of
utilisation to alter gut inflammation and pain.
Urology at Feinberg School of Medicine at Northwestern
University in Chicago. His research interests include the
molecular and neuronal mechanisms of acute and
Studies of the GI microbiome in Crohn’s disease also revealed
chronic pain of interstitial cystitis, chronic prostatitis/
diminished bacterial diversity among
chronic pelvic pain syndrome and urinary tract infections.
Firmicutes;
30
this both is
reminiscent of findings in obesity and suggests that bowel
Dr Rudick is a member of the Society for Neuroscience.
He received his PhD in neuroscience from Northwestern
inflammatory and/or pain conditions may exhibit altered
University in 2005 and trained as a National Institute of
microbiomes. Since bladder-associated pain is subject to modulation
Diabetes and Digestive and Kidney Diseases (NIDDK) Fellow. Dr Rudick identified the
by the gut through spatial integration, probiotic therapies that target
cellular and molecular bases of pelvic pain in murine neurogenic cystitis.
the GI tract may have efficacy for treating IC. Several studies of IBS
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