What causes interstitial cystitis / bladder pain syndrome?

With the exception of patients struggling with Hunner’s lesions, IC/BPS is now considered a complex neuromuscular disorder that can involve the bladder, the pelvic floor muscles and/or the nerves. It is often caused by injury to the pelvic floor muscles and/or bladder wall. Of course, your physician must rule out other potential conditions, particularly endometriosis, fibroid tumors that are pressing on the bladder, cystoceles, pelvic congestion syndrome, ketamine cystitis, radiation cystitis, sexually transmitted diseases, bladder and/or kidney stones and bladder cancer.

At the September 2016 ESSIC society meeting, Dr. Christopher Payne argued “There is an underlying assumption that this is a disorder of the bladder and is due to chronic inflammation. Both assumptions are generally false and bladder-centric treatments have poor response… It is abundantly clear BPS (without Hunner’s lesion) is most commonly a complex phenotype of neuromuscular-psychosocial disorder.”(1) He, and others, suggest that in addition to bladder and pelvic floor muscle injury, pudendal neuropathies, allergies and systemic pain disorders may also play a role in the development of IC.

Hunner’s Lesions Phenotype

Hunner’s lesions are distinct injuries or wounds in the bladder wall that trigger severe urinary symptoms and pain. These patients are often extremely diet sensitive and must follow IC diet suggestions to avoid irritating the wounds. Hunner’s lesions generally do not respond to typical IC therapies and require lesion specific treatments. The key question, however, is what triggers a lesion to develop. This is one of the key mysteries of IC and there are two dominant theories: a viral infection or a condition which triggers severe neuroinflammation, such as posterior fornix syndrome.

Viral Infection

The polyoma BK and Epstein-Barr viruses  have been found in the urine of patients with Hunner’s lesions. Researchers in Europe first made the connection in 2015 when they found the virus only in the urine of patients struggling with lesions. Polyoma BK has long been associated with the development of hemorrhagic cystitis in patients struggling with severe autoimmune disorders. The presence of a virus may explain why these patients rarely respond to traditional oral and bladder instillation therapies. In 2023, the first studies have been released exploring the use of antiviral therapies. Hunner’s lesions are also treated conventionally with fulguration, steroid injection and/or hyperbaric oxygen therapy.

Posterior Fornix Syndrome

A surprising cause of Hunner’s lesions emerged with the publication of a case study of a woman struggling with posterior fornix syndrome, essentially a broken ligament which allowed the uterus to rotate in place. Restoration of the proper position of the uterus with surgery resulted in a complete and total resolution of the lesion. Read the case study here! 

Bladder Wall Phenotype: Trauma, Estrogen Atrophy or Chronic Infection

For patients who struggle with pain as their bladder fills with urine, we look to three potential causes: chemical injury, estrogen atrophy and chronic infection.

Chemical Injury (chemocystitis)

The bladder, like any other part of the body, can be injured and usually this is due to chemical exposure. For example, patients who develop urinary symptoms while going through chemotherapy, struggle with the caustic effects of the medication on their bladder wall. Patients who consume large amounts of acidic beverages, such as coffees, green teas, sodas (especially diet) and energy drinks, can also develop bladder wall irritation over time. Thus, the therapeutic priority for this group of patients is to find and eliminate the irritant and give the bladder plenty of time (i.e. months) to heal. These patients must follow the IC diet to avoid damaging the healing tissue.

Estrogen Atrophy (GSM)

The bladder and urethra protects itself with a very thick coating of mucus which acts as a barrier between urine and the more fragile cells of the bladder wall. Unfortunately, that mucus is estrogen dependent. Thus, when a patient is young and have plenty of estrogen, they usually have a strong, thick coating. However, patients who are on stronger birth control, Lupron for the control of endometriosis, have had a total hysterectomy or who are simply aging have thinner and more fragile mucosal barriers. In essence, the bladders ability to protect itself is now compromised and urinary symptoms often develop over time and with the consumption of more acidic, irritating foods. This is known as estrogen atrophy or the genitourinary syndrome of menopause (GSM). Treatment is focused on providing topical estrogen (i.e. estradiol) to help these cells rebound and produce mucus, along with various strategies that can coat and protect the bladder wall. (i.e. chondroitin based supplements & bladder instillations). Ask your doctor to look at the quality and health of your skin.  Watch our video “The Estrogen Chat” featuring ICN Founder Jill 

Chronic Infection

When the symptoms of IC are virtually identical to those of a UTI, it’s only natural for men and women to assume that they have a UTI. Generally, though, urine cultures are negative.  In late 2022, Dr. Curtis Nickel proposed nine distinct phenotypes for IC, one of which is an infection-mediated subtype.  Dr. Nickel argued that there are patients who have a history of recurring UTI”s may be experiencing a “bladder hypersensitivity syndrome” secondary to the infection. While long-term antibiotic therapy is an option, Dr. Nickel suggests applying antibiotics directly to the bladder via bladder instillation.   It is also possible to have a fungal infection which, again, as typical urine culture would no grow out. This is where Next Generation DNA Urine Testing is ideal. It is a much more specific urine test that will identify all good bacteria, pathogenic bacteria and fungus in urine and  often does identify a potential infection. Learn more about Next Gen Testing at: bladderhealth.org

Pelvic Floor Phenotype

Many IC patients report that their symptoms began immediately after pelvic floor muscle trauma, including: childbirth, athletic injury, or riding a bicycle / motorcycle. One study found that 87% of participating women with IC had muscle pain consistent with pelvic floor dysfunction. Similar studies have also found pelvic floor dysfunction in men with chronic prostatitis.

Patients may not understand that tight muscles can directly influence and/or cause bladder, prostate and rectal symptoms. They can make urination, defecation and intimacy difficult and painful. Tight muscles near the urethra can trigger urethral burning and pain. Tight muscles near the rectum can cause rectal burning and discomfort. Blood flow through the pelvis and to the bladder may become restricted (aka ischemia). Tight pelvic floor muscles can squeeze certain nerves causing pudendal neuralgia or sciatica.  In these patients, the treatment priority is restoring normal muscle tone and function.

PFD patients may not experience pain as the bladder fills with urine. Their discomfort is often more chronic, with duller levels of consistent pain that can worsen with sitting. However, long-term pelvic floor patients often struggle with diet induced flares and bladder wall sensitivity  because the long-term tension has reduced blood supply to the bladder resulting in a more vulnerable bladder wall.

Widespread Pain  / Nervous System Dysregulation / Central Sensitization

For patients struggling with IC and other pain syndromes (irritable bowel syndrome (IBS), vulvodynia, prostatitis, chronic fatigue and anxiety disorder), an injured, dysregulated central nervous system is the root cause. In the 2011 American Urology Association Guidelines for IC/BPS, they suggest that “IC/BPS is a member of a family of hypersensitivity disorders which affects the bladder and other somatic/visceral organs.” For the majority of children who eventually develop widespread pain, this author included, a physical trauma in childhood is the root cause, such as a major physical accident. For others, it can be result of abuse or bullying that if unresolved, leaves the nervous system in perpetual “fight or flight.”  Therapeutically, our goal is to calm the nervous system and eliminate fight or flight with mind-body medicine techniques.

Other causes of NSD include chronic stress which forces the nervous system stays in a state of high alert, adverse childhood experiences (neglect, physical or emotional abuse, or living with a family member who has mental health or substance use issues).  Genetic factors can predispose individuals to a dysregulated nervous system (redheads are well known to have more sensitive nerves).  Poor diet, lack of physical activity, and inadequate sleep can disrupt the normal functioning of the nervous system. Caffeine and alcohol can overstimulate the nervous system and lead to dysregulation. A diet low in B vitamins, Omega-3 fatty acids, magnesium, and others, can contribute. Lastly, exposure to toxins in the environment, such as heavy metals, pesticides, mold, and certain chemicals, can negatively impact the nervous system. Stress at work, such as high stress or loud noise, also stresses the nervous system.

Pelvic Organ “Cross Talk”

Pelvic nerve pathways can also contribute to bladder irritation. Research studies have demonstrated that 40 to 50% of IBS patients have symptoms of IC while up to 52% of IC patients also have symptoms consistent with IBS. Bowel-bladder nerve “cross sensitization” was proven by Pezzone, who demonstrated that direct bowel irritation caused bladder irritation and vice versa. When long-term chronic bowel irritation occurred, some of the familiar symptoms of IC also occurred, such as increased frequency and decreased urinary volume.He determined that the outgoing (afferent) nerves of the bladder and the bowel combine at the dorsal root ganglia, providing ample opportunity for “cross talk.”

Dr. Pezzone believes that chronic pelvic pain can develop after an acute injury or chronic irritation to one of the pelvic organs (bladder, bowel, reproductive), nerves or perhaps even the skin. If the irritation/inflammation persists, the other organs and muscles then become involved through this “cross talk” sensitization pathway. Researchers and clinicians agree that treatment should be focused on calming and soothing every condition that is producing pain and/or discomfort. This also falls into subtype 5, functional somatic syndrome and/or central sensitization syndrome

Allergies

Dr. Curtis Nickel believes that there is a group of patients who struggle with systemic allergies that are also affecting the bladder. These patients struggle with respiratory, environmental and dietary allergies. He says they can be easily identified during a cystoscopy by gently poking the bladder wall with the tip of a flexible cystoscope to look for a “mucosal wheal-flare reaction.”  He suggests that these patients should follow a strict diet and use an antihistamine (hydroxzyine)  and/or cimetidine. The patients may also benefit from a typical rescue instillation.

Updated: November 15, 2023 – JHO

Created: January 4, 2017 – JHO

Author: Jill H. Osborne
Revised: January 14, 2017