In trying to prove XMRV link to interestitial cystitis I'm finding great info

[Annikki]

Hi, I'm new here and while I have another autoimmune disease, I'm startled by the parallels all these diseases have. Anyhow, my disease is called interstitial cystitis. It is an autoimmune condition specific to the bladder in human beings and felines. Don't think for 10 minutes that this disease is any less relenting than ME/CFS; unfortunately doctors think we are crackpots too and won't treat us. Wessely made his comments about us too and they are sticking. Me, I've lost everything just like you dear people can and do thanks to the medical bigotry which won't go away.

Interstitial cystitis or IC is like having a permanent urinary tract infection with no pathogen. You go to the bathroom well over 60 times a day. Your symptoms don't stop at night and sleep becomes impossible as a result. The pain is severe. We too give up, we too must fight for answers to why this happens. Our disease manifests many symptoms which are co-morbid to CFS- we too have shrunken adrenal glands (cats with IC have this too and there are studies about this- Google Tony Buffington for these), mitral valve prolapse, low blood volume. I have symptoms myself which match CFS but to a lesser degree. Yet my bladder renders life impossible for me because this disease is an autoimmune condition where the bladder lining is attacked as opposed to neurons. There are neurons in the bladder, FYI and IC is classified as neurological. I believe it fully is.

Now to the research discussion. I have been spending some time trying to write an article suggesting why testing IC patients for XMRV would be a good idea. Even without studying too hard there are obvious reasons to test it for XMRV. FMS, CFS/ME. Sjogrens, Lupus and more are co-morbid with IC. Strangely so is prostatitis . I say "strangely" because very few men get IC in the first place. Prostatitis is linked to the onset of prostate cancer- I read somewhere that XMRV causes inflammation in the prostate which sets the stage for cancer. Enough with simple, flimsy arguments.

I am aware the XMRV studies are being attacked somewhat relentlessly. Most of my research is using the premise it is XMRV causing IC, CFS, FMS and more. I hope XMRV is still a possible cause. Regardless, in an effort to pin down how XMRV could begin to cause the cascade of IC symptoms I am finding information which secures this autoimmune disease as having the same nature as other autoimmune disease.

What I've found in studying about bladder physiology in relation to IC and other conditions is the same issues- purinergic receptors, nerve cells and ATP abnormalities form the basis of IC symptoms. While surely this sounds very odd to a newbie to the topic, this is all very true. In the bladders of people with interstitial cystitis, there is an abnormally high amount of extracellular ATP. Most researchers are figuring that ATP has a signalling role, and this is very true in the bladder. Stretching a bladder cell can cause it to release ATP- other cells in the body release ATP due to physical changes. All human bladders release ATP during stretch- it is part of the way the nervous system detects if the bladder is full. In IC patients, this level of ATP is very high and studies have ruled out the other things like inability to re-uptake ATP.

I know very well that CFS/ME symptoms have a link to ATP too, and Dr. Light is doing some great work tying purinergic receptors which bind to ATP in CFS and FMS. His work is spot on in my opinion- that is because the pathology of IC is rooted in purinergic receptors too. This is where it gets ugly because I have far too many studies to list, but I'll give it a go.

My original idea is that XMRV in some way is modifying both purinergic receptors and ATP-binding cassettes. One list showed there are XMRV homologues to a few ATP-binding cassettes. I haven't linked the purinergic part to this yet. I'm going to have to read more about mitochondria and how ATP is produced and get a bigger picture of the entire ATP process in healthy people and us.

The interesting part of what I am sharing is that there have been a few new developments in IC research, one of which being a unique siaglogly copeptide found in IC patients urine. Right now my head is spinning over this because p53, a key cancer related gene has been found as the source of this unique siaglogly copeptide in IC officially named "antiproliferative factor (APF)."

It is findings like this which really make it hard for me to shelve XMRV (and I know full well this is a political issue so I'm not buying everything I hear).

Unfortunately, given the sheer enormity of information I'm sifting through right now, I'm going to have to share just dry data and a very brief theory statement. I'm learning about 3 different diseases in tandem, I am having to learn biochemistry as I go, and there are so many good articles out there. The good news is that all the information I'm finding fits together very, very well. I can't help but think we are all working to solve a collective mystery about a disease with different manifestations and is a politically hot item for some damned reason.

For starters, I'm going to share a good article about IC with good basic information and the least amount of Wessely school drivel inserted (yes, the disease is real!!): http://findarticles.com/p/articles/mi_m0FDN/is_4_8/ai_111303984/

Here is my old, fairly simple thesis:

Notes on IC and ATP


Studies have shown that when bladder epithelial cells are stretched they release ATP. In the bladders of people with interstitial cystitis, more extracellular ATP is released than in control patients.

Quote: (BMJ August 8th, 2009: 339:337-342)
(IC bladder uroepithelial cells released significantly higher concentrations of ATP (adenosine triphosphate) than control biopsies suggesting that ATP plays an important role in this syndrome. An investigation of cultured bladder epithelial cells showed that such cells have an abnormal, much higher concentration of ATP. This higher concentration of ATP decreases the ability of the bladder wall to conduct (channel) potassium ions which again indicates impaired potassium ion conduction is part of the pathology of interstitial cystitis.

Studies on ME/CFS have shown deficient ion channelopathy to be part of the pathology of ME/CFS. Some studies about ME/CFS and potassium conduction attribute this flaw to abnormal mitochondrial gene expression.

The BMJ article cited says studies on IC showing ATP increase and changes in potassium conduction as also resulting from abnormal gene expression.

I suggest the issue of ATP, potassium ion channelopathy as being the result of XMRV. Idiosyncratic production of ATP and its components such as purinergic receptors, ATP- binding cassettes (ABCs) and or ABC transporters is well documented in many other autoimmune diseases and can be fully attributed to the source of most IC symptoms.

I hypothesize these abnormalities are the result the presence of XMRV in interstitial cystitis, and occur through many different mechanisms, including viral mimicry and others.

The hypothesis that XMRV likely cause of significantly high release of ATP in bladder urothelial cells is supported by observed defects in ATP-binding cassette transporters, where XMRV viral mimicry of proteins is likely to have occurred..

About ATP Binding Cassettes
ATP-binding cassette transporters are members of a protein superfamily that is one of the largest and oldest proteins.
ABC transporters are transmembrane proteins that utilize the energy of adenosine triphosphate (ATP) hydrolysis to carry out certain biological processes including the translocation of various substrates across membranes and non-transport related processes such as translation of RNA and DNA repair. ABCs transport a wide variety of substrates across extra and intracellular membranes, including metabolic products, lipids and sterols, and drugs. Proteins are classified as ABC transporters based on the sequence and organization of their ATP-binding cassette (ABC) domain(s). ABC transporters are involved in tumor resistance, cystic fibrosis, bacterial multi drug resistance and a range of other inherited human diseases.

One of these diseases is Pseudoxanthoma Elasticum (PXE), a hereditary connective tissue disease in which proteoglycans have altered properties. In pseudoxanthoma elasticum there are abnormalities which show some relevance to interstitial cystitis. Both diseases show a relationship with sulfated glycosaminoglycans. The only difference is that in PXE, an inherited genetic defect in an ATP-binding cassette transporter identified as ABCC6/MRP6

The idea that ABCC6/MRP6 is the cause of PXE was tested in 2003 in Italy.
Proteoglycan metabolism in PXE was studied by Francesca Maccari, Dealba Gheduzzi and Nicola Vopi at the University of Modena, in Modena, Italy.

In this study, the researchers measured sulfated glycosaminoglycans in the urine of people with PXE, people carrying the disease and healthy controls. Sulfated glycosaminoglycans are what compose the mucosal lining of the human bladder, known as the GAG layer. The GAG layer is deficient in IC patients because the bladder epithelial cells which secrete GAG become compromised and cease to serve their function.

The glycosaminoglycans this study on PXE tested for were chondriotin sulfate disaccharide and heparan sulfate disaccharide. Note also that to treat interstitial cystitis, heparin sulfate is instilled into the bladder to augment the defective GAG layer. In Canada and elsewhere outside the U.S., chondriotin sulfate has been used with even better results than heparin sulfate as a bladder instillation, to help IC patients in those places.

In PXE 34% less of the polysaccharides were detected in the urine of PXE individuals, than controls or unaffected carriers of the genetic defect.

It is worth noting that the commonality between IC and PXE patients may extend beyond glycosaminoglycans being abnormally low. On the revealing of the genome for XMRV, a comparison of what human proteins the XMRV retrovirus mimics finds a link between the virus and ABC transporters.

A retrovirus is different from normal viruses. Normal viruses only have their DNA transcribed into RNA in the host, and the RNA is then translated into a protein. A retrovirus functions in a different way, which more adeptly inserts its genome into human DNA. Retroviruses have their RNA reverse-transcribed into DNA, which is then integrated into the hosts genome and then undergoes the usual transcription and translation processes to express the genes carried by the virus.

How this relates to the issue of XMRV and autoimmune diseases, its speculated that XMRV creates proteins which mimic those in the human body. The idea is that the fake DNA created by the virus initiates a response from the human immune system. Some believe that the human immune system becomes confused from the retroviral proteins which mimic its own proteins. This leads to the unending attack from the body on its own tissue.

There is an ATP-binding cassette associated with the viral mimicry of XMRV infection. It is called ABCC9:

It is known as EAW96452.1. This is an ATP-binding cassette of the subfamily C (CFTR/MRP), member 9, isoform ABCC9. XMRV GAG- PRO-POL was found to mimic the natural properties of this ABC.

Note that ABCC6 in PXE where altered levels of glycosaminoglycans is very closely related to ABCC9. Both of these ATP-binding cassettes are of the subfamily MRP.


However, a link between this possibly compromised ATP binding cassette know as ABCC9 and interstitial cystitis goes further than its proximity in nature to ABCC6.
Here is what the genome mapping project says about ABCC9

ABC proteins transport various molecules across extra and intra cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein is thought to form ATP sensitive potassium channels in cardiac, skeletal and vascular and non-vascular smooth muscle. Protein structure suggests a role as the drug-binding channel modulating subunit of the extra pancreatic ATP-sensitive potassium channels. Mutations in this gene are associated in cardiomyopathy dilated type 10. Alternative splicing results in multiple transcript variants.

Now we go back to the idea the BMJ article expressed; the idea that come IC pain comes from inability for the bladder epithelial cells in IC patients to channel potassium ions. Also issues involving dysfunctional bladder smooth muscle activity parallel a possible defect in ABCC9 as a causative agent in IC symptoms. Bladder spasms and pelvic floor muscle issues become clearer when the idea of viral mimicry of ABCC9, or other ABCs.

Potassium channeling function by ABCC9 also alludes to the co-morbidity of mitral valve prolapse in interstitial cystitis patients. This too is another trait common to both IC and CFS/ME. Furthermore, defective cassette binders have been linked to the lack of energy proliferation in the bodies of CFS patients. Potassium channeling has also been linked to the pain of fibromyalgia.

The studies of Dr. Light bind the idea that a defect in receptors in the muscle fiber of fibromyalgia patientsreceptors which detect levels of ATP used or not used by the body which is part of the role which ABCs and or ATP sensors like purinergic receptors play in the pathology of that disease.

This makes good enough sense to me. Looking at the many studies which show the prevalence of extracellular ATP in both human and feline IC patients, and furthermore, studies which demonstrate a clear link between extracellular ATP and pain in the human bladders support the idea of ATP being at the root of IC abnormalities.

Source: Augmented Extracellular ATP Signaling in Bladder Urothelial Cells from Patients with Interstitial Cystitis Study by Yan Sun and Toby C. Chai, Division of Urology, Department of Surgery, University of Maryland School of Medicine.
http://apjcell.physiology.org/content/290/1/C27.full


Studies regarding extracellular ATP causing pain in human bladders extend beyond IC research. There was a study performed in Sweden demonstrating that extracellular ATP and the purinergic receptors P2Y are responsible for the inflammatory response in human bladders exposed to the E coli bacteria. Or to put in simple terms, ATP and purinergic receptors which bind to ATP are responsible for the pain and inflammation in the common urinary tract infection.

Bladder stretching itself also causes the bladder epithelial cells to excrete ATP. Studies have ranged from hypothesizing that extracellular ATP serves a role as a signaling mechanism in the human body, where its release upon stretching the human bladder generates the feeling and urge to go. I blame the inability of ABC transporters to serve their role in transporting substrates through intra and extracellular membranes as being part of why some substances irritate IC bladders and cause no sensation of pain in people with normal bladder tissue.

I attribute the experience of interstitial cystitis as being largely dependent upon defective ATP-binding cassette behavior.

I suggest exercise works as an IC therapy because it uses up the extracellular ATP.

I will show proof for my argument in referring to a study which show that extracellular ATP is responsible for other IC anomalies, including the defect where tryptophan in IC patients is broken down into kynurenine over serotonin and melatonin.

The indoleamine 2,3, dioxygenase pathway is the formal name for the modification of tryptophan into various other chemicals.

Here is a study proving that extracellular ATP effects the maturation of human dendritic cells (immune cells), affecting the indoleamine pathway:
Source: Thrombospondin and indoleamine 2,3 dioxygenase are major targets of extracellular ATP in human dendritic cells. Frdrick Marteu, Nathalie Suarez Gonzalez, David Communi, Michel Goldman, Jean-Marie Boeynaems, and Didler Communi. http://bloodjournal.hematologylibrary.org/content/10612/3860.full

This article states:

Extracellular adenosine triphosphate affects the maturation of human dendritic cells, mainly by inhibiting T-helper (Th 1) cytokines, promoting Th2 cytokines and modulating the expression of costimulatory molecules. In this study we report that adenosine triphosphate can induce immunosuppression through its own action on DCs, defining a new role for extracellular nucleotides. Microarray analysis of ATP-stimulated human DCs revealed an inter alia a drastic up-regulation of 2 genes encoding mediators involved in immunosuppression: thrombospondin-1 and indoleamine.."

It is known that bladder stretching causes cells to release ATP. This is one way physical changes alone can alter bladder surface biochemistry.

Furthermore, the amounts of extracellular ATP becomes more prevalent upon mechanical stretch can be reduced by chemicals already present in the bladder. In a study by Sun Y and Chai TC at the Division of Urology at the University of Maryland School of Medicine, both heparin sulfate and dimethyl sulphoxide (DMSO) reduce the higher levels of stretch activated ATP release in the bladders of people with interstitial cystitis.

The idea supported by the results of this study is that bladder epithelial cells (bladder urothelial cells or BUCs) are able to detect levels of ATP and rely upon ATP as a chemical messenger of sorts.

Another thing which stresses the importance of studying the role of ATP in interstitial cystitis is that ATP plays a major role in generating the disease symptoms in other autoimmune disorders:

So you ME/CFS people don't feel left out of this research, know that this is oh, so relevant to solving your problem too. Again, I'm finding good material:

Purinergic Irregularities and Autoimmune Disease

Source: Review: Potential Retrovirus Causal Paths in CFS and FM Rev 2. Laurence G. Felker, Reno, NV (775) 852-9326.

Disregulated immune, endocrine and neurological systems are well known. Adenosine triphosphate (ATP) processing has been clearly shown to be abnormally regulated in CFS and a test is now available which correlates severity of the condition with ATP processing. Evidence also exists which shows other abnormalities in purine regulation contribute to this condition. If extracellular ATP, adenosine diphosphate (ADP) and adenosine monophosphate (AMP) are elevated while adenosine (ADO) is deficient, then multiple effects will occur. Nociceptive input via the P2X3 receptors is elevated. Endocrine disruption can occur. Cellular energy levels are lower accounting for fatigue. Since ADO promotes sleep, its lower levels may account for the sleep disturbances found in CFS.

Here are some of my notes:

ATP Cassette Binders, Purinergic Receptors; Role in pathogenesis of Autoimmune and Relation to XMRV Infection

ABC cassettes are related to XMRV infection
ABCE1 ATP-binding cassette, subfamily E (OABP), member 1, [Homo sapiens]
Also known as RNASEL1; RNASELI, RLI, OABP, ABC38
The protein encoded by this gene is a member of the subfamily of ATP binding cassette transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This protein is a member of the OABP subfamily. Alternatively referred to as the RNase L inhibitor, this protein functions to block the activity of ribonuclease L. Activation of ribonuclease L leads to inhibition of protein synthesis in the 2-5A/RNasel L system, the central pathway for viral interferon action. Two transcript variants encoding for the same protein have been found for this gene.

Genomic context:
Chromosome: 4; Location 4q31

ABCC9 ATP-binding cassette, subfamily, C (CFTR/MRP), member 9 [homo sapiens]
Also known as SUR2, ABC 37, CMD1O; FLJ36852
Te protein encoded by this gene is a member of the superfamily of ATP-binding cassette transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinctive subcategories (ABC1, MDR/TAP, ALD, OABP, GCN20, and White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance.
This protein is thought to form ATP-sensitive potassium channels in cardiac, skeletal, and vascular and non-vascular smooth muscle. Protein structure suggests a role as the drug-binding channel modulating subunit of the extra-pancreatic ATP-sensitive potassium channels. Mutations in this gene are associated with cardiomyopathy dilated type 1O. Alternative splicing results in multiple transcript variants.

Genomic Context:
Chromosome 12; Location 12p12.1

ABCC6/MRP6 transporter
In Pseudoxanthoma Elasticum (PXE) ABCC6 has been found to alter the properties of sulfated glycosaminoglycans.
Researchers believe the presence of altered GAGS in PXE results from an inherited genetic defect in the ABC transporter called ABCC6/MRP6. PXE is a hereditary connective tissue in which proteoglycans have altered properties. PXE is a disease which shares commonalities to interstitial cystitis because in PXE chemical alterations to the sulfated glycosaminoglycans heparan sulfate and chondriotin sulfate occur. In one study the sulfated glycosaminoglycans in the urine of PXE



ABCB1 or MDR1 P-glycoprotein
ABCB1 is involved in other biological processes for which lipid transport is the main function. It is found to mediate the secretion of the steroid aldosterone by the adrenals and its inhibition blocked the migration of dendritic immune cells, possibly related to the outward transport of the lipid platelet activating factor (PAF). It has also been reported that ABCB1 mediates the transport of cortisol and dexametasone, but not of progesterone in ABCB1 transected cells. MDR1 can also transport cholesterol, short-chain and long chain analogues of phosphatidycholaine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), sphinogomyelin (SM), and glucoasylerimide (Glc)Cer.

The human ABCB (MDR/TAP family) is responsible for multi-drug-resistance, (MDR) against a variety of structurally unrelated drugs.

The problem of autoimmune disease patients of having an abnormally high resistance to medications may possibly be explained by abnormalities in ABCB1.
This is a eukaryotic ABC protein. Although most eukaryotic ABC transporters are effluxers, some are not directly involved in transporting substrates. In the cystic fibrosis transmembrane regulator (CFTR) and in the sulfonylurea receptor, ATP hydrolysis is associated with the regulation of opening and closing of ion channels carried by the ABC protein itself or other proteins.
Human ABC transporters are involved in several diseases that arise from polymorphisms in ABC genes and rarely due to complete loss of function by ABC proteins. Such diseases include Mendealian diseases and complex genetic disorders such as cystic fibrosis, adrenoleukodaystrophy, Pseudoxanthoma elasticum, and more.
(Source: Wikipedia, ABC transporters article)
XMRV Viral homologues to human
Proteins.
ABCC9/ EAW96452.1 ATP binding cassette, sub family C (CFTR/MRP, member 9, isoform.
This protein is thought to form ATP sensitive potassium channels in cardiac, skeletal and vascular and non-vascular smooth muscle.
Homologous proteins
[LE* D*IFP*RF MP*+]
ATP2C1 EAW79217.1 ATPase, Ca+ transporting, type 2C, member 1, isoform CRA_a[Homo
This magnesium dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium, XMRV ENV.

Here now are some studies and articles which lay out how there is something very unique going on with ATP and what it binds to in interstitial cystitis. One very interesting tidbit worth knowing is that abnormal breakdown of tryptophan to kynurenine; a process that happens in my disease, yours and fibromyalgia has been linked to extracellular ATP and its affects on dendrite development. Yes, I'm not going to be wasting your time- I'm sharing information which seems to be getting so fruitful, I am struggling to get through all of it.

Oh, BTW, here's that article about Antiproliferative Factor, p53 and IC: "P53 regulates two ATP-generating pathways; p53 is gene responsible for Antiproliferative Factor (APF) in interstitial cystitis
Differential Utilization of two ATP-regulating pathways is regulated by p53
by Wissam Assaily and Samuel Benchimol, Department of Biology, York University, Toronto, Ontario, Canada.
http://www.sciencedirect.com/science/article/pii/S15356108060019166

 

[currer]

Hi Annikki

You have done a lot of research.

Why not just get yourself tested by the WPI. If you are positive you can share your ideas with them.

They might be interested to find out what you have discovered.

 

[svetoslav80]

Never seen a longer post. Hope you find a treatment.

 

[ukxmrv]

Annikki,

I am XMRV+ but don't have IC. That doesn't mean much as I've heard other PWME mention IC before and it seems to be common.

Maybe set up a poll and ask XMRV+ if they have IC?

There is a formal poll somewhere else on the internet but I have lost track of where it is (will post the link if I find it).

 

[pamb]

Hello Annikki,

First, I'm sorry you have a reason to be here. IC is, as you have said, truly horrible to live with.

Please do come back and let us know if you are XMRV + or - through the WPI- if of course you can get together the money to be tested.

Here is an odd coincidence - or not - to add to your very scientific analysis. My husband has had ME for 10 years now, his daughter, now in her late 40's, had horrible IC for many years but it seems to have calmed down somewhat. However, in the last ten years she has really suffered from FM. I was thinking the hereditary link may support a possible A+B XMRV likelihood for them both, now that you have added IC to the list, I sure wonder if the odds have increased.

Fingers crossed the blood working group have some positive results from the current phase. It is a long wait for Lipkin, or so it seems.

 

[Annikki]

Sorry for the length of the thread but everything is really horrible for me now and i wanted to get something posted. Sorry about that. I don't have money to go get tested; I'll be lucky to eat this month. This is what lack of social support and medical care does. This sucks because I haven't been getting enough sleep between symptoms and doing a herculean effort of trying to make it while unable to work and more. There is stuff I want to do but there is no way for it to happen and it makes me feel sad. On the IC forums there isn't discussion of or awareness of the politics and research which occurs here. I just wanted to share what I had but there is just too much for me to do. Worse, I write like crap when I don't have sleep.

 

[its ME Jeff]

Very interesting! I am XMRV+ and suffer with M.E. My wife suffers from I.C. She has not been tested for XMRV.

 

[GaryK]

I cant afford the XMRV test either BUT I can tell you that I am an ME person who does have the I.C. Symptoms.
Thank you very much for your hard work and posting it here Annikki.

I'm finding this very interesting....and please keep the Good work going as much as you can in the time you can afford.

GaryK

 

[Annikki]

Very interesting! I am XMRV+ and suffer with M.E. My wife suffers from I.C. She has not been tested for XMRV.

Ah, the contagion issue. A friend of mine is sick with ITP and this is another autoimmune disease linked to XMRV by the WPI. I wonder about the contagion issue and she's knows I'm researching XMRV. At best we drank out of the same coffee cup. I still wonder if IC people could be carrying this virus too. Given the location of the urethral opening, sexual transmission model comes to mind.

More to the point, the location of the prostate gland makes you wonder about XMRV and sexual transmission. Chronic prostatitis is strangely co-morbid to interstitial cystitis- almost exclusively women get IC. Just part of why I can't help but think XMRV and IC are related: http://www.ichelp.org/Page.aspx?pid=355

I'll repost the full list of conditions that occur in tandem to IC from the Interstitial Cystitis Association website:

Allergies and Sensitivities
Celiac Disease
Chronic Fatigue Syndrome
Chronic Prostatitis
Endometriosis
Fibromyalgia
Irritable Bowel Syndrome
Lupus
Pelvic Floor Dysfunction
Pudendal Neuralgia
Sjogrens Syndrome
Vulvodynia

Individuals with allergies, migraine headaches, endometriosis, irritable bowel syndrome, asthma, or sensitive skin may have a greater chance of developing IC. And, some studies have reported that IC patients are as much as 100 times more likely than the general population to have irritable bowel syndrome.
Vulvodynia, a syndrome marked by various painful vulvovaginal symptoms, is the fourth most common IC-related condition. It is thought that a common defect in the bladder and the vaginal tissues may contribute to both conditions.
Individuals already suffering from IC may also have a greater chance of developing fibromyalgia or chronic fatigue syndrome.
IC patients have been shown to be 30 times more likely than the general population to have systemic lupus erythematosus.
More recent research has revealed that IC may also be connected with certain other chronic conditions, such as panic attacks and pelvic floor dysfunction.

 

[Hip]

I believe I had overactive bladder (OB), which is very similar to interstitial cystitis (IC). The main difference between OB and IC seems to be that there is pain involved with IC, but not with OB. However, these conditions are otherwise very similar.

I had OB for many years, but it has abated a little now that I also developed chronic fatigue syndrome, for some reason.

My OB started out of the blue, and from being a person with really excellent bladder control (I would often not need to go at all through my 9 to 5 working day), I suddenly became hostage to the bathroom, having to rush with incredible urgency to wee, even if my bladder was just full. Many times this urgency to wee came on so fast and intensely, that I have had to screech the car to a halt, jump out, and wee behind a tree!

The urgency to urinate is caused by strong muscular contractions of the bladder, due to nerve actions that cannot be controlled or suppressed (as I am sure you know).

My OB symptom came on suddenly, within a week or so, after dating a new girlfriend. I think that this was probably because I caught a respiratory virus/bacterium from her during kissing (or perhaps more likely, from oral sex, with the microbe entering the bladder via the urethra).

Incidentally, a similar thing thing happen to me 12 years later, when I caught a respiratory virus again from kissing someone I was dating, which lead to a horrible viral sore throat appearing the next day after the first date, a sore throat which never went away; and this sore throat virus soon plunged me in CFS but my CFS is another story, let's focus on OB/IC here.

Now, no viruses or bacteria have yet been found in the bladders of OB/IC patients (although I understand that some cases of OB are caused by infections treatable with antibiotics). Why might this be? Why have the infectious agents presumed to be causing IC and OB not been found as yet?

One likely explanation for not finding any microbe in the bladders of OB/IC patients is that OB/IC may be caused by a "stealth" virus like coxsackievirus B. Coxsackievirus B is strongly linked to autoimmune conditions, so it fits the bill for OB/IC very well.

Most people with CFS know that coxsackievirus B has a stealth mode of infection that is hard to detect, as very few viral particles are created. Instead of normal viral particles being produced, in a chronic coxsackievirus B infection, you find that there is mostly just RNA from the coxsackievirus B. This RNA infection is the stealth mode of coxsackievirus B. The existence of this stealth mode of coxsackievirus B is why, in regular lab tests, infections could not be found in many CFS patients, even though their symptoms indicated that there was apparently an ongoing infection. Now is it known and understood that coxsackievirus B does have a stealth mode, and indeed, this stealth infection can now be tested for these days.

So coxsackievirus B is really the perfect candidate as a potential cause of OB/IC, as:

(a) it can cause a stealth infection that cannot be easily detected (and we know that the pathogen causing OB/IC has not yet been detected)
(b) coxsackievirus B is strongly linked to autoimmunity (OB/IC is an autoimmune condition)
(c) coxsackievirus B loves to live and replicate in the mucous membranes (the lining of the bladder is a mucous membrane)

For more info on coxsackievirus B, see the work of Dr John Chia (there's lot of info about Chia on this site; refs: 1, 2).

These RNA stealth infections of coxsackievirus B and other enteroviruses are also called "non-cytolytic enterovirus", "non-cytopathic enterovirus", or "defective enterovirus" infections.


Autoimmunity Caused By Infections

Coxsackievirus B is a chief suspect not only for causing CFS, but also a chief suspect for causing the autoimmune damage to that leads to type 1 diabetes.

However, coxsackievirus B / enterovirus are not the only types of microbes that have been linked to autoimmunity:

Autoimmune diseases are also associated with the viruses Epstein-Barr virus, cytomegalovirus, parvovirus B19 and HIV; and the bacterium Mycobacterium tuberculosis. (Source: List of Chronic Human Diseases Linked To Infectious Pathogens).

But all these (apart from coxsackievirus B) are easily detectable, so presumably they would have been found in the bladders of OB/IC patients, if they were the cause of OB/IC.


An Effective Treatment of Overactive Bladder (OB) and Interstitial Cystitis (IC) ??

Some years ago I made a fortuitous discovery that the herb Ruta graveolens significantly improved my OB. In fact, even when I stopped taking Ruta graveolens, the improvement this herb made in my OB symptoms still remained for months.

Ruta graveolens has both anti-microbial and anti-inflammatory properties, and either of these may be the reason why it worked for me.

This herb is something you may want to try. I would be very interested to hear if you got similar good results from taking Ruta graveolens. Note that Ruta graveolens should not be used during pregnancy due to the risk of miscarriage.

 

[Hip]

Why Ruta graveolens treats interstitial cystitis / overactive bladder so well

Update:

I think just discovered why the herb Ruta graveolens (common rue) works so well for interstitial cystitis / overactive bladder: I think it's because this herb contains a substance called 5-methoxypsoralen that alters potassium channel fucntion in cells (ref: here), and potassium channels are implicated in interstitial cystitis (ref: here).

Definitely worth trying the herb, for anyone with interstitial cystitis / overactive bladder.

 

[warriormom]

Very interesting. My daughter had the IC symptoms and diagnosis before CFS/ME onset. Is the Ruta Graveolens available at GNC?

 

[Hip]

Ruta graveolens - buying guidelines

Very interesting. My daughter had the IC symptoms and diagnosis before CFS/ME onset. Is the Ruta Graveolens available at GNC?

Ruta graveolens is a bit of an obscure herb, so you you'll probably have to buy it online.

I suggest buying Ruta graveolens as bulk powder, as it is much cheaper than way:

Ruta graveolens powder (US)
Ruta graveolens powder (UK)

You can also buy Ruta graveolens in tinctures, but it is best to go for bulk sizes (like or a liter or more), as smaller size tinctures work out expensive, given that you need to take 2 ml (= 0.07 fluid ounces) or more each day.

Ruta graveolens tincture (US)
Ruta graveolens tincture (UK)

Avoid any homeopathic formulations of Ruta graveolens, as there is no Ruta graveolens whatsoever within such formulations you might as well drink pure water (which what homeopathic formulations are).

 

[Hip]

Will Ruta graveolens (common rue) also help treat CFS?

Since interstitial cystitis seems to be a predisposing factor to CFS, it may be that a long term treatment using Ruta graveolens may also improve CFS symptoms (for people that have interstitial cystitis / overactive bladder as well as CFS).

It's extremely interesting that cellular potassium channels are implicated in interstitial cystitis.Potassium channel dysfunction is also a part of the picture of CFS (see Cort's article on channelopathy in CFS).

This makes me think that this potassium channels connection may be the reason interstitial cystitis can predispose an individual to CFS. Interstitial cystitis is already messing with your potassium channels, so perhaps you are already halfway to CFS when you have interstitial cystitis.

Then if you go on to catch a nasty virus like coxsackievirus B, which itself messes with various ion channels (ref: here), including the potassium channel, it is perhaps no surprise that IC + coxsackievirus B leads to CFS.

So Ruta graveolens's effect on potassium channels may be of general benefit in CFS.

 

[warriormom]

Ruta graveolens is a bit of an obscure herb, so you you'll probably have to buy it online.

I suggest buying Ruta graveolens as bulk powder, as it is much cheaper than way:

Ruta graveolens powder (US)
Ruta graveolens powder (UK)

You can also buy Ruta graveolens in tinctures, but it is best to go for bulk sizes (like or a liter or more), as smaller size tinctures work out expensive, given that you need to take 2 ml (= 0.07 fluid ounces) or more each day.

Ruta graveolens tincture (US)
Ruta graveolens tincture (UK)

Avoid any homeopathic formulations of Ruta graveolens, as there is no Ruta graveolens whatsoever within such formulations you might as well drink pure water (which what homeopathic formulations are).

Great info...I will have my daughter give it a try.