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.

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.

#1 – Bladder Wall Trauma or Injury

Some cases of IC/BPS are caused by trauma or injury to the bladder, such as a bladder infection. In one study, a proven UTI was initially identified in 18 to 36% of women though subsequent urine cultures are negative. (2) Chemical exposure, such as from ketamine use (3) or chemotherapy (cyclophosphamide, ifosfamide), can irritate the bladder lining and, severe cases, lead to permanent damage.(4) Some patients believe that their excessive consumption of sodas (diet & regular sodas), coffees and/or alcohol is the cause of their IC. These patients generally experience worsening symptoms as their bladder fills with urine that feels better after the bladder is emptied.

When the bladder is injured, urine can penetrate deeply into the bladder wall where it can provoke nerves, cause mast cells to release histamine and cause widespread irritation. These patients may also experience a secondary effect – pelvic floor muscles tightening in a “guarding reflex.”

Treatment priority in this group of patients is to protect the bladder wall and support healing. Tight muscles may also need to be treated with physical therapy and/or muscle relaxation.

Special note for menopausal women

With menopause, women experience estrogen atrophy resulting in a dramatic thinning of the mucous in the bladder, urethra, vulva, vagina and mouth. With less mucous, the bladder and urethra are more easily irritated by urine. This can also play a role in their bladder symptoms. Ask your doctor to look at the quality and health of your skin. If you are showing signs of estrogen loss, you may want to consider using an estrogen cream to improve the quality and health of your skin. Watch our video “The Estrogen Chat” featuring ICN Founder Jill 

#2 – Pelvic Floor Injury & Dysfunction

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.(5) Similar studies have also found pelvic floor dysfunction in men with chronic prostatitis. (6)

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. 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.

#3 – Genetics

A genetic connection has been observed in a small percentage patients who have first degree relatives also diagnosed with IC.(7) In some families, bladder sensitivity can go back several generations.

#4 – A Systemic Neurosensitivity Disorder

For patients struggling with IC and other pain syndromes (irritable bowel syndrome (IBS), vulvodynia, prostatitis, chronic fatigue and anxiety disorder), a systemic condition may underly their health problems. 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.” (8)

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. (9) 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.(10) 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

#5 – AntiProliferative Factor (APF)

One of the biggest research breakthroughs IC/BPS, the antiproliferative factor (APF). It appears to block the normal growth of the cells that line the inside wall of the bladder.(10) APF may be part of an inflammatory reaction. Researchers have been unable to develop a reliable diagnostic urine test using APF as a marker.

#6 – Polyoma BK Viral Infection

The polyoma BK virus has 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. (11) Polyoma BK has long been associated with the development of hemorrhagic cystitis in patients struggling with severe autoimmune disorders. Though this research is new, the presence of a virus may explain why these patients rarely respond to traditional oral and bladder instillation therapies.