What is Interstitial Cystitis/BPS?

Causes

(Updated with 2025 Canadian IC/BPS guidelines & Dr. J. Curtis Nickel’s framework)

Nickel JC. Managing interstitial cystitis/bladder pain syndrome in female patients: Clinical recipes for success. Can Urol Assoc J. 2022 Dec;16(12):393-398. doi: 10.5489/cuaj.8055. PMID: 36656690; PMCID: PMC9851219.

Research and clinical experience have shown that IC/BPS is not a single disease but a collection of symptom patterns (phenotypes). 

Dr. Curtis Nickel is a leading Canadian researcher and clinician in interstitial cystitis (IC/BPS) and he has proposed a new way of understanding IC/BPS by identifying nine potential phenotypes within the patient community. Through decades of caring for patients he observed that there is no single “right” treatment for IC/BPS. As he explains, when asked how to treat a specific patient, his response often changed based on that individual’s unique clinical picture. This insight highlights a crucial reality for patients: a rigid, step-by-step… one-treatment-at-a-time approach often fails to address the complexity of living with IC/BPS.

Many patients fall into more than one category and phenotypes may change over time.

Identifying which phenotype(s) apply to you can help guide more targeted and effective care.

1. Inflammatory IC/BPS (Hunner Lesion IC)

This subtype includes patients with visible bladder inflammation or Hunner’s lesions seen during cystoscopy. Dr. Nickel recommends:

• Cauterization (fulguration) of Hunner’s lesions… repeated if necessary
• After successful cauterization, steroid injections (triamcinolone) directly into the lesion (total dose not exceeding 80 mg)

For early or mild recurrences, he suggests a classic rescue bladder instillation containing:

• Lidocaine (for pain relief)
• Triamcinolone (to reduce inflammation)
• A bladder lining agent such as:
  • Chondroitin sulfate
  • Heparin sulfate
  • Sodium hyaluronate

For patients who do not respond to these approaches, oral cyclosporine has shown success in select cases.

2. Infection-Mediated IC/BPS

This is a newer phenotype not widely recognized in older classification systems.

Dr. Nickel proposes that some patients with a history of recurrent urinary tract infections (UTIs) develop a bladder hypersensitivity syndrome following infection, even when standard urine cultures are negative.

Treatment considerations may include:

• Careful evaluation to avoid unnecessary long-term antibiotics
• Bladder instillation of antibiotics rather than systemic use
• Preventative strategies for recurrent infection

Dr. Nickel has also shared promising research on a UTI vaccine (MV140), which significantly reduced UTIs in studied patients.

He believes the future of UTI diagnosis may involve next-generation DNA urine testing, though more research is still needed.

3. Neurogenic Hypersensitivity IC/BPS (Central Sensitization)

Patients in this group often have chronic overlapping pain conditions, such as:

• IBS
• Fibromyalgia
• Migraines
• Endometriosis

In these cases, pain is driven by nerve hypersensitivity rather than bladder damage alone.

The goal of treatment is to calm the nerves in both the bladder wall and the central nervous system.

Treatment approaches may include:

• Low-dose neuromodulating medications (e.g. amitriptyline)
• Bladder instillations that support the GAG layer, such as:
  • Chondroitin sulfate
  • Heparin sulfate
  • Sodium hyaluronate
• Lidocaine may be added if pain is a prominent symptom

4. Multiple Allergies / Mast Cell–Associated IC/BPS

These patients often have:

• Environmental allergies
• Respiratory allergies
• Food sensitivities

Dr. Nickel notes they can sometimes be identified during cystoscopy by a mucosal wheal-and-flare reaction, seen when the bladder wall is gently stimulated.

Management strategies may include:

• A strict elimination diet
• Antihistamines such as hydroxyzine
• Acid-reducing agents like cimetidine
• Rescue bladder instillations when needed

5. Pelvic Floor Pain–Dominant IC/BPS

Patients with this phenotype show signs of:

• Pelvic floor muscle tension
• Trigger points
• Muscle guarding or spasm

Effective treatment focuses on muscle health, including:

• Localized heat
  
• Stretching and relaxation
  
• Pelvic floor physical therapy
• Skeletal muscle relaxants (e.g. vaginal diazepam suppositories)

Pelvic floor muscle physical therapy is now considered a gold standard therapy for IC/BPS patients and research studies have found it to be more effective than oral medications and/or bladder treatments for many patients. Nickel emphasizes that pelvic floor physiotherapy should be performed by specialists trained in pelvic floor manipulation.

If pain is one-sided or follows nerve pathways, nerve blocks may be required. Pelvic floor BotoxA may also be helpful, though it was not routinely used in his clinic.

6. Primary Storage Symptom Syndrome

Some IC/BPS patients experience urgency and frequency primarily to avoid the pain caused by bladder filling.

Dr. Nickel suggests:

• Treating pain first
• Then introducing medications that target urgency and frequency, such as:
  • Antimuscarinics (e.g. solifenacin)
  • Mirabegron (which may help both pain and urgency)

Bladder training is considered essential to help gradually increase bladder capacity.

As a last resort:

• BotoxA may provide short-term symptom relief but carries a risk of urinary retention
• Sacral neuromodulation may help urgency and frequency, though it may not significantly improve pain

7. Urethral Pain Syndrome

This phenotype is one of the most challenging to treat.

Patients experience pain localized to the urethra, which may be:

• Constant
• Episodic
• Associated with urination
• The only symptom present

Treatment options may include:

• Topical lidocaine gel (2–5%)
• Vaginal estrogen to improve tissue health
• Local or oral amitriptyline
• Phenazopyridine
• Diazepam
• Periurethral nerve blocks

8. Associated Sexual Pain

Pain with intimacy must be addressed in sexually active patients.

Assessment should first determine:

• Is pain coming from the bladder?
• Pelvic floor?
• Vagina or vulva?

Priority treatments may include:

• Pelvic floor physical therapy
• Topical lidocaine
• Estrogen therapy to improve vaginal skin health

9. IC/BPS Flares

Some patients experience sudden worsening of symptoms, known as flares.

Common triggers include:

• Diet
• Menstruation
• Stress
• Other infections
• Inflammatory or painful conditions
• Intimacy

Flares can last from hours to several days. If flares correspond with menstruation, it could be related to endometriosis and a referral to an endometriosis specialist who is trained is excision, not ablation, should be considered.

Common flare-management strategies include:

• Diet modification
• Increasing water intake
• Stopping irritating supplements (e.g. cranberry, vitamin C)
• Stress reduction
• Heat or cold therapy
• Short-term antihistamines
• Phenazopyridine

Why treatments may fail (and it’s not your fault)

• Wrong phenotype targeted
• Treating bladder only when muscles/nerves are involved
• Missing comorbidities (endo, IBS, vulvodynia)
• Over-reliance on antibiotics

These evolving subtyping systems provide a more tailored approach to diagnosing and treating IC/BPS patients and sheds light on the need for personalized care and addressing the diverse range of symptoms and underlying causes.