Interstitial Cystitis

Aloha!
Sorry I didn't write last week but we were in the OR until 10 pm one night and 8pm the other. Nobody ever said this kind of surgery was easy, but it sure is challenging.
I thought I'd write about interstitial cystitis today. IC as we call it, is the second leading cause of pelvic pain in women, behind (you guessed it) endo. Some studies show as high as 80% of women with chronic pelvic pain (CPP) had evidence of bladder involvement as a cause of pain, sometimes by itself and sometimes accompanying other pain generators such as endo or levator muscle spasm. IC causes pain in the central pelvis that can radiate out towards the groin or back to the sacrum. Some people feel it deeper, like at the top of the vagina. Typically the pain is worse with a full bladder, so these patients tend to void often, and they usually have some degree of urgency and frequency because the bladder wall doesn't like being stretched out. As you can imagine, intercourse can be miserable, although sometimes changing positions so the bladder is out of the way can make it tolerable.
One of the biggest problems with IC is that it can take years for patients to get a diagnosis. IC falls in the gap between gynecology and urology, with both specialties trying to pawn the patients off on the other. This is partially because of a lack of training about IC that hopefully is being rectified, and partially because many docs don't like taking care of chronic pain patients. It is true that patients with chronic pain can be difficult to care for, some requiring a lot of time and hand-holding and some with narcotic abuse issues, but I'll tell you what, there is nothing as satisfying as helping someone who's been in pain for a long time. Most patients don't want drugs, they want pain relief, and when you help them accomplish that, they are so grateful that for me anyway, that's all I need to keep me going. The other thing about pelvic pain is that it usually doesn't show up on ultrasounds, CT scans, or lab tests. Doctors that are good at diagnosing pelvic pain have to rely on listening to the patient and doing a focused, methodical exam, then use their powers of deductive reasoning and gut intuition to come up with an idea of what's causing the pain, and what to do about it. Doctors aren't used to making diagnoses this way these days, without confirmatory imaging studies, so it takes a special person with an interest in pelvic pain and compassion and empathy for the patients to be good at it.
Nobody is quite sure yet just what causes IC, but the leading idea is that of "neurogenic inflammation". What happens is that a painful stimulus that continues over time, (whether from endo or levator spasm or essentially anything in the pelvis) eventually can cause reverse transmission of nerve impulses from the spinal cord on down to the pelvis. When these stimuli reach the end of the nerve (for IC the bladder nerves) certain substances (like histamine, cytokines, and prostaglandins) are released from mast cells that cause swelling and nerve irritation. These inflammatory mediators that the mast cells release then cause more nerve irritation via other mediators that upregulate the pain fibers (nerve growth factor and substance P), eventually causing a vicious circle of pain. Another theory is that there are breaks in the mucousy lining of the bladder that protects the cells from all the irritants that the kidneys are excreting. These two theories are not mutually exclusive and likely the neurogenic inflammation causes the breaks in the lining (the technical term is the "gag layer" because it is composed of glycosamino glycan, or gag, which is a big huge sugar molecule).
It is logical based on the above theory of neurogenic inflammation why there is a significant overlap between those with endo and those with IC, but this doesn't explain why women without endo (or men, for that matter) get IC. Going back to the painful stimuli part of the theory, it is possible that any pain generator in the pelvis can induce the backwards nerve transmission and thereby neurogenic inflammation. It is a well-known fact that we are in an epidemic of abuse in this country. Whether by parents, partners, or strangers, nearly one third of all US women admit to having been abused at some point in their life. Women with IC have a higher percentage of abuse than those without - nearly half of IC patients admit to being the victim of abuse. The reason this is significant is that any abuse, but especially sexual abuse can cause a prolonged spasm of the levators, the muscles of the pelvic floor (the muscles used in Kegel exercises). Prolonged muscle spasm eventually causes increased firing of the pain sensing nerves in the muscles, which starts the vicious cycle. There is a lot of cross-innervation in the pelvis, which means that nerves to the bladder, pelvic floor, upper vagina, rectum, and any other pelvic site come from the same nerve root as it exits the spinal canal. They also interconnect like an LA freeway, joining and separating often on their way to the end-organ. This allows for 2 things to happen - the first is that a painful stimulus can start anywhere in the pelvis and cause the neurogenic inflammation in another pelvic location (this is also the proposed etiology for vulvar vestibulitis, but we won't get into that today). The second is that "neural cross-talk", or this sharing of nerve fibers between various organs in the pelvis, is probably why there are patients with IC, irritable bowel syndrome, and fibromyalgia all at the same time.
IC can be treated in a variety of ways, but none are "curative". Hydrodistention (blowing up the bladder with water under anesthesia) is both diagnostic and therapeutic. When either ulcers (only seen in 10-15% of pts) or glomerulations (small areas of bleeding from surface blood vessels) are seen after hydrodistention, then IC is present. Hydrodistention also is known to give some relief for a few months afterwards. Bladder instillations are my favorite treatment because they work quickly and pretty effectively. For people with significant pain, instilling lidocaine (a local anesthetic) and heparin (rebuilds the mucous lining) can give them immediate pain relief that can last for several days. Initially the instillations are 3 times a week, but with time the interval can be stretched out to a week or 2. Elmiron is a drug designed specifically for IC. It also rebuilds the lining like heparin does, but it takes 3-6 months to see a benefit, which is why I like to start with both oral Elmiron and bladder instillations. Tricyclic antidepressants work well to depress the pain fiber activation, essentially putting a damper on the hypersensitive pain nerves. Since chronic pain does cause depression, having a side effects of a little mood elevation and improved sleep doesn't hurt, either. Some people advocate antihistamines, specifically atarax, because it stabilizes the mast cells so they don't release their nasty inflammatory mediators, but I find that most people can't tolerate the sleepiness it causes.
I think there's a lot we don't yet know about pain, why some patients have minimal disease and a lot of pain, why some patients have a ton of disease and a little pain, and why some people develop new pain after their old pain was fixed. The good news is that a lot of research is being done to identify places in the inflammation cascade as well as the nervous system where interventions can be made. Right now we have some drugs that definitely can help women with IC and those with chronic pelvic pain (non-endo related), but I think that within the next 5-10 years some significant advances will be made. (for those of you that missed the previous articles on excision, that's the cure for endo). Just think, it was only 20 yrs ago or so when they called IC a "disease of hysterical women" and told them to see a shrink!
There is hope on the horizon, and if we're lucky it will come soon.
Take care and have a great week. Don't forget, send me your questions and ideas for next week's blog. My record review are free until further notice, and you get two for the price of one!
Dr. Mos