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Interstitial Cystitis & Endometriosis: Two Sides of the Same Coin?

Author Melissa Malena covers Interstitial Cystitis & Endometriosis: Two Sides of the Same Coin? on BackTable OBGYN

Melissa Malena • Feb 2, 2024 • 223 hits

Interstitial cystitis and endometriosis are often comorbid, as they are both hypothesized to cause pain via central sensitization and crosstalk mechanisms. Patients with both conditions often experience high levels of chronic pain and see a multitude of practitioners without relief. Dr. Jocelyn Fitzgerald, urogynecologist with the endometriosis clinic at UPMC Magee in Pittsburgh, advocates for a multidisciplinary approach to holistically treat these complex patients.

This article features excerpts from the BackTable OBGYN Podcast. We’ve provided the highlight reel in this article, but you can listen to the full podcast below.

The BackTable OBGYN Brief

• Mast cell activation from inflammation in the bladder or uterus upregulates signaling pathways in efferent neurons, releasing tryptases. The tryptases then damage junctional proteins, further inflaming the bladder and making it susceptible to other irritants.

• The positive feedback loop of neuroinflammation and mast cell activation is the mechanism of visceral hyperalgesia, an inappropriately increased pain response to gastrointestinal stimuli.

• Endometriosis and interstitial cystitis are whole-body diseases and require specialty collaboration to provide comprehensive care. Specialty collaboration includes the fields of urogynecology, behavioral health, internal medicine, gastroenterology and pain management.

Interstitial Cystitis & Endometriosis: Two Sides of the Same Coin?

Table of Contents

(1) Central Sensitization in Interstitial Cystitis & Endometriosis

(2) A Multidisciplinary Approach to Interstitial Cystitis

Central Sensitization in Interstitial Cystitis & Endometriosis

According to Dr. Fitzgerald, the neuroinflammation associated with conditions like interstitial cystitis, endometriosis, and irritable bowel system is related to central nervous system sensitization. Afferent ganglia from the irritated organ send signals of increasing intensity and frequency to the spinal cord. Efferent neurons then increase inflammation through mast cell activation, furthering the positive feedback loop. These efferent neurons increase inflammation not only within the target organ but within all the organs that the particular spinal area innervates. In interstitial cystitis, mast cell activation upregulates signaling pathways within the bladder through tryptase release, disrupting junction gap proteins and inducing pain sensations through A-delta and C autonomic fibers. Dr. Fitzgerald believes central sensitization turns organ-specific maladies into full-body diseases, creating the associated system-wide symptoms.

[Dr. Amy Park]
I've heard of the somatic referred pain, but I've never heard of this visceral referred pain and this crosstalk. How does it work? Does it go to the ganglia?

[Dr. Mark Hoffman]
Dumb it down for the listeners like me.

[Dr. Amy Park]
I've heard Susie's talk about central sensitization. I know that they run together in terms of the IC, IBS, vulvodynia, all these disorders, but how does it not affect the rest of your body? Does it just go into your pelvic nerves and the ganglia there?

[Dr. Jocelyn Fitzgerald]
That's exactly what happens. This is how I knew I was not built to be a lab researcher when I was in med school. Again, my two mentors-- Pam Moalli was one of my great mentors. She's a very famous urogynecologist for anyone who's listening and currently my boss. I did research with a gastroenterologist and a urologist in order to study female pelvic pain.

We would inject these radio-fluorescent markers into the colon. It was blue. I remember it was a blue luminescent dye and it would get taken up by the afferent nerves in the colon and then we would inject yellow dye into the bladder and then we would-- This was so insane, this dissection we would do to get out the dorsal ganglia of the lumbosacral nerve roots of these rats. It was so small.

Then slice them up and then look at them and look and see where the dye tracker had gone. We would find that a really large number of these ganglion neuron roots had both blue and yellow dye in them. They synapsed literally on the same exact nerve root. Then they would look and see is now this message from the colon, this inflammation that's telling all the afferent nerves in the colon like, "We're on fire. Help us."

It would go back to the spinal cord and then it would, in these shared neurons, send out this inflammatory signal that would affect the neighboring organs that shared the same nerve supply, and then those nerve endings we would also do all these histologic slices of it, would recruit all these mast cells to the nerve endings specifically that had the crosstalk happening.

The nerves that are shared with the other angry organ summon all this-- It puts out all this TNF alpha and all these mast cells and just brings all this angry inflammation to its little endings and then it starts to upregulate all these other signaling pathways that makes your bladder very overactive and painful. It also kicks and makes the urothelium very leaky because the mast cells are releasing all these triptases and they're making all of the junctional proteins go to crap and then all of a sudden the bladder is a mess and in tatters and it's very susceptible to other irritants when it fills but also from its lamina propria side.

It just has all these mast cells in it now and they're going crazy and all of the afference that feel pain, like A-delta and C-fibers get really upregulated.

[Dr. Amy Park]
I find that fascinating because it's really not part of what is taught in medical schools. We all hear about referred pain and the diaphragmatic irritation causing shoulder pain and those kinds of things but we don't hear about the visceral aspect of the autonomic fibers, which I find fascinating.

[Dr. Jocelyn Fitzgerald]
So interesting. I can't even explain it well.

[Dr. Mark Hoffman]
It's not well understood? Is it that it's new? Is it that no one cares? All the above?

[Dr. Jocelyn Fitzgerald]
I think that it actually is understood fairly well. I did this research over a decade ago and worked with all these really brilliant people who were like, "Oh, yes, this is the thing." It's a pretty well-known mechanism of visceral hyperalgesia and crosstalk. There's a few different mechanisms for it, but it's a pretty well-established thing. I think it's just that no one knows how to reverse it.

Once the horse has left the barn, how do you downregulate these mast cells, how do you downregulate all these pain receptors that have suddenly come to the surface? How do you reverse central sensitization? I don't think we know how to do that because that is also so closely tied to the emotional stress that has been triggered in real people who experience these symptoms.

What starts out maybe as an infection or maybe an autoimmune condition or maybe another disease in another organ, suddenly you have these real-world symptoms, you have distress over it, which probably kicks up your cortisol or who knows what else. Then all of a sudden, your whole body is programmed to feel pain and it's like, how do you put that horse back in the barn? That's why they try drugs like Lyrica and all this other stuff, but it becomes a full-body disease. Endometriosis, when it's a painful disease, is not just like a gynecologist's disease. It is like a full-body thing. I think that's why we've just not been very successful at treating it.

Listen to the Full Podcast

Painful Bladder Syndrome with Dr. Jocelyn Fitzgerald on the BackTable OBGYN Podcast)
Ep 38 Painful Bladder Syndrome with Dr. Jocelyn Fitzgerald
00:00 / 01:04

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A Multidisciplinary Approach to Interstitial Cystitis

Dr. Fitzgerald advocates for a multi-specialty approach to interstitial cystitis patient management. Pelvic physical therapy is particularly beneficial and Dr. Fitzgerald’s practice has in-clinic physical therapists that help to reduce the time and travel burden on patients. On endometriosis clinic days, all members of the team meet and discuss each case. The team includes representatives from urogynecology, behavioral health, pain management, imaging, emergency medicine, internal medicine, and soon, a gastrointestinal expert. They follow a tumor-board-like model, combining specialties in an in-person and virtual format, crafting next steps and emergency plans. This multidisciplinary approach allows the team to holistically care for these complex patients and ensures that these patients receive comprehensive management that targets each potential issue.

[Dr. Jocelyn Fitzgerald]
We actually had this clinic today. The endometriosis center at Pitt was already established when I showed up being run by MIGS and they were seeing patients alongside pelvic floor PT at the same time plus or minus behavioral health, a psych piece. I am obviously very passionate about adding my urogyn expertise and bladder pain expertise and so I really wanted to be involved with the help of Nicole Donnellan, who you should probably have come on here because she's brilliant and awesome.

Anyway, twice a month, we split the clinic in half. Dr. Donnellan's template is in the morning, my template is in the afternoon. In the morning, I have administrative time, but any patients that would benefit from me seeing them for a consultation for their bladder or for pelvic floor trigger point injections, I will go in and see that patient after she has seen them alongside pelvic floor physical therapy. They see the patient together and if the patient wants to get physical therapy that day without having to have multiple exams. We all have a discussion about the patient, they go across the hall to the physical therapy offices and they have physical therapy right then and there.

Sometimes I will even do pelvic floor trigger point injections, and then they'll go get PT immediately after their injection, which a really interesting paper came out last year showing that patients actually do have an improved response to PT if they have injections right beforehand.

[Dr. Mark Hoffman]
Before each visit?

[Dr. Jocelyn Fitzgerald]
Not each visit, but depending on the patient. If there's someone who just is not tolerating PT really well, I don't know, their pain is in a really specific area, we work with PT. PT often will see the patient first and then say, "I think this would be somebody that would respond really well to an injection before their visit," or, "If you could do injections first and then send them back to us instead of the other way around." I leave that to the PT's judgment. They're really good and they know when someone is not just going to cold turkey, be able to handle physical therapy day one.

[Dr. Mark Hoffman]
It's such an important part of it to be able to have PT, to have that relationship. I'm very lucky that our PTs are downstairs from where we are. I was part of bringing pelvic floor PT to UK because it was such a big deal at Michigan where I trained. People were using it, it wasn't like I brought it, but it was something that I was part of building it where it was because there was so much demand. They're right downstairs and the letters they write and we can communicate. Managing patients together is wonderful. It's amazing you've got them across the hall, though, and in the same visit.

[Dr. Jocelyn Fitzgerald]
Yes, same visit. It's awesome. Then in the middle of the day at lunch, we have a multidisciplinary meeting with behavioral health about patients that, in particular, need extra. It's almost like a tumor board where we are all part virtual, part in-person. We had it today and talked about some really challenging patients. That has been really great. There's still pieces that we're trying to add. We're trying to recruit a GI person. That's a whole other podcast, like how little training GI gets in gynecology and female pelvic medicine. We interviewed and are really trying to recruit someone who's interested in doing that from a GI perspective.

[Dr. Mark Hoffman]
GI, colorectal surgery, both?

[Dr. Jocelyn Fitzgerald]
Mostly GI. For really bad endo lesions maybe, but I really think on the medical side, you really need a good GI person who knows a lot about motility, understands how IBS and endometriosis interact, understand defecatory disorders and pelvic floor spasm, puborectalis spasm, dyssynergic defecation, that kind of thing. That's really helpful. They're not in the clinic, but we do have people from pain medicine, also some internal medicine people who are super close with PM&R. I have an emergency medicine doc who helps me make complex care plans for these patients, very similar to as if they were a sickle cell patient.

We have regular meetings where we talk about when they come to the ER with a flare, what are we giving them. Then our chronic pain specialist helps in those meetings as well, coming up with those plans. We have a lot of friends in the pot. We're still working on it but that's what I spend my time doing in that clinic, coordinating that care for these patients who have a lot of medical PTSD from just not being believed and going from doctor to doctor to doctor or you aren't talking to each other. My role is to talk to them, all for them. I write a lot of notes and messages and emails, but I think it helps.

[Dr. Mark Hoffman]
It's incredible. It's not an easy thing. Having people buy into what you're doing is, I think, my favorite part of this job, is getting people who are equally excited as you are trying to solve complicated problems. Being in a university seems to attract some of those. Some of us who like solving hard problems, doing hard puzzles, but finding other colleagues. I've got a colorectal surgery colleague who I do all my tough endo cases with and it's just my favorite days. In my fiber program, we build an IR doc, just like catching up. Imaging is a whole other thing. I don't know if you guys do much with that with radiology, but we've been very lucky too to do that.

Just having these partners solve these hard problems, but what can it do for patients to have that buy-in? I plea for docs out there with skills and ability to reach out and think about how you can contribute to women's health and these complex diseases that need more time, more energy, more effort outside of your own little wheelhouse. That's where I've had the most fun and had the most success, I think. Kudos to you and your group over there.

[Dr. Jocelyn Fitzgerald]
Oh, thank you. I really think those colorectal surgeons, all these specialists, I always tell them, I'm like, "This is an area, do you want to become famous in your field? Go back to your meetings with your colleagues and talk about how you manage this." There is nothing in the GI literature about how to manage IBS caused by endometriosis. That is not a thing in their IBS guidelines. It's probably like [chuckles] the majority of IBS in women is probably related to endo in some way or some huge piece of it and they don't even think about it. It doesn't even cross their mind.

When I tell them, their mind is blown. I'm like, "You could become really famous really fast in your field for basically writing guidelines that don't exist." The last thing I want to say is people who care, I don't want to undersell how important it has been to have administrators in our department who care deeply about women's health, people who have literally masters in healthcare administration. Most of our administrators are women, and they went into healthcare administration to help do women's health from that angle.

That is one of the most powerful things I've ever witnessed because we go into their office and say, "This is a population of patients who are suffering and they're falling between the cracks. We need you to help us set up pathways between psych, between the ER, between GI." They work on those things behind the scenes so that we can actually have resources and be profitable.

It's been shown in studies that you can generate a lot of new business for your healthcare system if you have these clinics set up. They have a lot of buy-in with us too and they phone in actually to our multidisciplinary meetings as administrators to see how they can support the clinic. That is the reason the clinic exists is because they are so devoted.

Podcast Contributors

Dr. Jocelyn Fitzgerald discusses Painful Bladder Syndrome on the BackTable 38 Podcast

Dr. Jocelyn Fitzgerald

Dr. Jocelyn Fitzgerald is a urogynecologist and pelvic reconstructive surgeon and an assistant professor at University of Pittsburgh Medical Center in Pennsylvania.

Dr. Amy Park discusses Painful Bladder Syndrome on the BackTable 38 Podcast

Dr. Amy Park

Dr. Amy Park is the Section Head of Female Pelvic Medicine & Reconstructive Surgery at the Cleveland Clinic, and a co-host of the BackTable OBGYN Podcast.

Dr. Mark Hoffman discusses Painful Bladder Syndrome on the BackTable 38 Podcast

Dr. Mark Hoffman

Dr. Mark Hoffman is a minimally invasive gynecologic surgeon at the University of Kentucky.

Cite This Podcast

BackTable, LLC (Producer). (2023, November 9). Ep. 38 – Painful Bladder Syndrome [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.

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