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Interstitial Cystitis / Bladder Pain Syndrome

Interstitial cystitis / bladder pain syndrome (IC/BPS) is chronic bladder and/or pelvic pain, pressure, or discomfort of greater than six weeks' duration accompanied by urinary urgency and frequency, in the absence of identifiable causes.[1][2] The 2022 AUA Guideline emphasizes an individualized, multimodal treatment approach rather than a tiered algorithm — treatments are grouped by modality (behavioral/non-pharmacologic, oral medications, intravesical, procedures, major surgery) and combined based on phenotype and response.[3]

Definition and Classification​

Diagnostic criteria​

ESSIC definition (accepted by ICI 2010): chronic pelvic pain, pressure, or discomfort >6 months perceived as bladder-related, with at least one other urinary symptom (urgency, frequency), after exclusion of confusable diseases.[1]

AUA Guideline basic diagnostic principles:[3]

  • Symptoms present ≥6 weeks with documented negative urine cultures
  • Document voiding frequency, urgency, pain location/severity
  • Baseline assessment using GUPI, ICSI/ICPI, or VAS
  • One-day voiding log to establish low-volume frequency pattern
  • Brief neurological exam; evaluate for incomplete bladder emptying
  • Cystoscopy and urodynamics not required for uncomplicated presentations

Phenotypic classification — Hunner vs non-Hunner​

IC/BPS is increasingly recognized as two distinct clinical entities.[2][5][6]

FeatureHunner-lesion IC/BPSNon-Hunner IC/BPS
AgeOlder (mean diff +6.7 years)Younger
PathologyPancystitis, B-cell abnormalities, epithelial denudationMinimal histological changes
Bladder capacityReduced (mean diff −113 mL)Preserved
Urinary frequencyHigher (mean diff +3.2/day)Lower
Urinary biomarkersElevated CXCL10, NGF, IL-6, IL-8, MIF, luminal NOLower inflammatory markers
Comorbid pain syndromesLess commonMore common (fibromyalgia, IBS)
Treatment responseResponds to fulguration, triamcinolone, cyclosporine AVariable; multimodal

Epidemiology​

Prevalence:[1][7][8]

  • Women: 2.7–6.5% (symptom surveys); 1.08% (chart-confirmed)
  • Men: 0.66% (chart-confirmed); approximately 10–20% of female prevalence
  • US overall: 0.87% (95% CI 0.32–1.42)
  • Estimated 3.3–7.9 million US women with IC/BPS symptoms
  • Only 9.7% of symptomatic women report an IC/BPS diagnosis — substantial underdiagnosis

Demographics:[1][9]

  • Female : male ratio approximately 10 : 1
  • Peak onset 40–50 years
  • Associated with depression, anxiety, sexual dysfunction, reduced QoL

Pathophysiology​

The etiology is incompletely understood; several mechanisms likely co-exist and interact.[10][11][12]

  1. Urothelial dysfunction / GAG layer deficiency — defective glycosaminoglycan barrier allows urinary solutes (especially potassium) to penetrate the bladder wall[10][11]
  2. Mast cell activation — increased mast cell infiltration with histamine release[9][10]
  3. Chronic inflammation — persistent inflammatory state with elevated cytokines[11][12]
  4. Oxidative stress — reactive oxygen species impair bladder function through multiple pathways[11][12]
  5. Neurogenic inflammation — C-fiber activation, substance P release, peripheral neural upregulation[4][10]
  6. Autoimmune dysregulation — B-cell abnormalities, particularly in the Hunner-lesion phenotype[2][6]
  7. Central sensitization — spinal cord changes producing chronic neuropathic pain[4]

Diagnosis​

Basic assessment (clinical principle):[3] careful history, physical exam, urinalysis and culture; exclude infections and confusable disorders; document symptoms characteristic of IC/BPS.

Cystoscopy indications:[3]

  • Should be performed when Hunner lesions are suspected (expert opinion)
  • Consider in patients >50 years (higher odds of Hunner lesions)
  • Consider in patients who fail conventional therapies
  • Not required for routine diagnosis in uncomplicated presentations

Validated assessment instruments:

  • O'Leary–Sant Interstitial Cystitis Symptom Index (ICSI)
  • O'Leary–Sant Interstitial Cystitis Problem Index (ICPI)
  • Genitourinary Pain Index (GUPI)
  • Visual Analog Scale (VAS) for pain
  • Voiding diary (minimum 1 day)

See the Assessment Tools & Questionnaires page for detail.

Behavioral and Non-Pharmacologic Treatment​

Self-care and lifestyle (clinical principle)[3]​

  • Fluid management (restriction or additional hydration)
  • Dietary modification — avoid bladder irritants
  • Heat/cold application to bladder or perineum
  • Stress management, meditation, imagery
  • Bladder training with urge suppression
  • Avoid tight-fitting clothing; manage constipation

Dietary triggers and supplements​

Avoid:[14][15] citrus, tomatoes, coffee, tea, carbonated drinks, alcohol, artificial sweeteners, spicy foods, high-potassium foods, vitamin C supplements.

May help:[15] calcium glycerophosphate (Prelief), sodium bicarbonate.

Intensive systematic dietary manipulation produces significant improvement in ICSI, ICPI, and pain scores at 3 months and 1 year.[14]

Pelvic floor physical therapy — Grade A (Standard)[3][16]​

Appropriate manual techniques should be offered to patients with pelvic floor tenderness. Kegel-type pelvic floor strengthening should be avoided — the muscles are typically hypertonic, not weak.

Appropriate techniques: myofascial release, trigger point therapy, soft tissue massage, connective tissue manipulation, muscle contracture lengthening.

RCT evidence:[16] myofascial PT vs global therapeutic massage — 59% vs 26% response rate (p = 0.0012); pain, urgency, and frequency improved in both groups.

Oral Medications​

AUA Guideline Statement 14 (Option; Grade B–C): amitriptyline, cimetidine, hydroxyzine, or pentosan polysulfate may be administered — listed alphabetically, no hierarchy implied.[3][17]

AgentMechanismDosingEvidenceKey considerations
AmitriptylineTCA; anticholinergic, antihistamine, analgesic25–75 mg qhsBICSI reduction; anticholinergic side effects
Pentosan polysulfate (PPS)GAG-layer restoration100 mg TIDBOnly FDA-approved oral agent; maculopathy risk
HydroxyzineH1 antihistamine; mast-cell stabilizer25–75 mg qhsCSedation; may help sleep
CimetidineH2 blocker400 mg BIDBLimited evidence; may reduce pain
Cyclosporine AImmunosuppressantIndividualizedOff-labelBest efficacy in meta-analysis; significant toxicity

Network meta-analysis (Di et al. 2021):[18]

  • Cyclosporine A — superior for ICSI, ICPI, and VAS pain
  • Amitriptyline — significant ICSI reduction (MD −4.9)
  • Certolizumab pegol (investigational) — ICSI MD −3.6

PPS maculopathy — safety alert​

PPS is associated with a progressive, vision-threatening maculopathy.[3][19][20][21]

Clinical features:[19][21][22]

  • Prolonged dark adaptation; difficulty reading; blurred vision
  • Hyperpigmented macular clumps on fundus exam
  • Distinctive autofluorescence abnormalities on multimodal imaging
  • May progress even after drug cessation
  • Dose-dependent (cumulative exposure)

FDA-aligned screening:[3]

  • Detailed ophthalmologic history before initiation
  • Baseline retinal exam in patients with preexisting eye conditions
  • Retinal exam within 6 months of starting treatment
  • Periodic retinal exams while on treatment
  • If pigmentary changes develop, reevaluate risks/benefits

Intravesical Instillations​

AUA Guideline Statement 16 (Option; Grade C): DMSO, heparin, and/or lidocaine may be administered.[3]

AgentMechanismProtocolEvidenceNotes
DMSO 50%Anti-inflammatory, analgesic, muscle-relaxant, mast-cell stabilization50 mL, 15–20 min dwell, weekly × 6Grade COnly FDA-approved intravesical; garlic odor
LidocaineLocal anesthetic1–2% solution, 20–30 min dwellGrade BShort-term relief; alkalinization increases penetration
HeparinGAG-layer restoration10,000–40,000 UOff-labelOften combined with lidocaine
Hyaluronic acidGAG-layer restoration40 mg weekly × 4–6Off-labelEuropean use; limited US data
Chondroitin sulfateGAG-layer restorationVariableOff-labelOften combined with HA

DMSO meta-analysis (Li et al. 2025, 554 patients):[24] ICSI decreased by 5.59 points; DMSO + triamcinolone produced greater pain and nocturia improvement than DMSO alone; both groups showed significant increase in bladder capacity.[23]

"Cocktail" instillations often combine DMSO with heparin, hydrocortisone or triamcinolone, sodium bicarbonate, and lidocaine or bupivacaine.[3]

warning

DMSO enhances absorption of other substances — this creates potential for lidocaine toxicity when both are included in a cocktail.[3]

Procedures​

Hydrodistension (Option, Grade C)[3]​

Cystoscopy under anesthesia with low-pressure, short-duration hydrodistension. Allows inspection for Hunner lesions, stones, tumors; mild distension makes Hunner lesions easier to identify. Can provide clinically significant relief. Temporary post-procedure symptom flare is common. Multiple procedures do not progressively reduce bladder capacity.

Hunner lesion treatment (Recommendation, Grade C)[3]​

When Hunner lesions are identified:

  • Fulguration with electrocautery
  • Triamcinolone injection (40 mg)
  • Combination

Improvement is typically measured in months after a single procedure; symptoms recur and periodic retreatment is the rule. Multiple electrocauterizations do not significantly diminish bladder capacity.

Intradetrusor botulinum toxin A (Option, Grade C)[3]​

May be offered if other treatments have not provided adequate improvement. Symptom relief typically lasts several months. Common adverse events: dysuria, straining to void, elevated PVR, CISC requirement. Patients must accept the possibility of intermittent self-catheterization. Injection sites vary (trigonal, lateral, posterior walls).

Sacral neuromodulation (Option, Grade C)[3][25][26][27]​

Not FDA-approved specifically for IC/BPS, but many patients meet frequency/urgency indications and respond. Less effective for pain than for frequency/urgency.

Meta-analysis (Wang 2017, 583 patients):[25] significant pelvic pain reduction (WMD −3.99); durable symptom and QoL benefit. Long-term cohort data confirm sustained improvement in refractory patients.[26][27]

Major Surgery​

Reserved for severe, refractory cases after all other options are exhausted. Requires extensive counseling — pain can persist after cystectomy because of central sensitization.[1]

OptionEffect on capacityEffect on pain
Augmentation cystoplastyIncreasesNot reliably improved
Supratrigonal cystectomyMarkedly reduced (trigone preserved)Variable
Urinary diversion ± cystectomyDivertsMay or may not eliminate pain

Irreversible; shared decision-making and multidisciplinary input (pain, psychiatry, PT) are essential.

Emerging Therapies​

Active investigation in pharmacologic and device-based avenues:[1][28]

TherapyMechanismStatus
Certolizumab pegolAnti-TNF monoclonal antibodyPhase 2/3 trials
Hyperbaric oxygenIncreased tissue oxygenationLimited evidence
CannabinoidsAnalgesic, anti-inflammatoryInvestigational
Intravesical liposomesProtective coating against inflammationInvestigational
NGF inhibitorsAnalgesic (neural modulation)Investigational
Sustained intravesical release systemsExtended drug deliveryIn development

Treatment Algorithm Summary​

The AUA 2022 approach is modality-based rather than tiered:[3]

  1. All patients — education, self-care, behavioral modifications
  2. Pelvic floor tenderness — manual physical therapy (avoid Kegels)
  3. Suspected Hunner lesions — cystoscopy → fulguration and/or triamcinolone if present
  4. Oral medications — amitriptyline, hydroxyzine, cimetidine, or PPS (with maculopathy counseling)
  5. Intravesical — DMSO, heparin, and/or lidocaine (alone or in combination)
  6. Procedures — hydrodistension, botulinum toxin A, sacral neuromodulation
  7. Major surgery — augmentation, supratrigonal cystectomy, diversion (refractory only)

Core principles: treatment is individualized; shared decision-making is essential; multimodal approaches are often required; phenotyping (Hunner vs non-Hunner) guides therapy.

Comorbidities​

IC/BPS frequently co-occurs with other chronic pain and functional conditions:[1][12][15]

  • Irritable bowel syndrome
  • Fibromyalgia
  • Chronic fatigue syndrome
  • Vulvodynia
  • Chronic headache / migraine
  • Temporomandibular disorder
  • Depression and anxiety

This overlap supports common mechanisms (central sensitization, chronic inflammation, oxidative stress) and a multidisciplinary treatment approach.[13]

See Also​

References​

1. Imamura M, Scott NW, Wallace SA, et al. "Interventions for Treating People With Symptoms of Bladder Pain Syndrome: A Network Meta-Analysis." Cochrane Database Syst Rev. 2020;7:CD013325. doi:10.1002/14651858.CD013325.pub2

2. Akiyama Y, Homma Y, Maeda D. "Pathology and Terminology of Interstitial Cystitis/Bladder Pain Syndrome: A Review." Histol Histopathol. 2019;34(1):25-32. doi:10.14670/HH-18-028

3. Clemens JQ, Erickson DR, Varela NP, Lai HH. "Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome." J Urol. 2022;208(1):34-42. doi:10.1097/JU.0000000000002756

4. Nambiar AK, Eylert MF, 't Hoen LA, et al. "Bladder Disorder of Function." Chapter 23 in Campbell-Walsh-Wein Urology.

5. Lai HH, Pickersgill NA, Vetter JM. "Hunner Lesion Phenotype in Interstitial Cystitis/Bladder Pain Syndrome: A Systematic Review and Meta-Analysis." J Urol. 2020;204(3):518-523. doi:10.1097/JU.0000000000001031

6. Zhu L, Ke H, Wang Q, Xu K, Chen X. "Multi-Omics Profiling Reveals Distinct Pathogenic Mechanisms in Hunner and Non-Hunner Interstitial Cystitis Subtypes." Sci Rep. 2025;15(1):26536. doi:10.1038/s41598-025-12010-w

7. Anger JT, Dallas KB, Bresee C, et al. "National Prevalence of IC/BPS in Women and Men Utilizing Veterans Health Administration Data." Front Pain Res (Lausanne). 2022;3:925834. doi:10.3389/fpain.2022.925834

8. Berry SH, Elliott MN, Suttorp M, et al. "Prevalence of Symptoms of Bladder Pain Syndrome/Interstitial Cystitis Among Adult Females in the United States." J Urol. 2011;186(2):540-4. doi:10.1016/j.juro.2011.03.132

9. Dawson TE, Jamison J. "Intravesical Treatments for Painful Bladder Syndrome/Interstitial Cystitis." Cochrane Database Syst Rev. 2007;(4):CD006113. doi:10.1002/14651858.CD006113.pub2

10. Karamali M, Shafabakhsh R, Ghanbari Z, Eftekhar T, Asemi Z. "Molecular Pathogenesis of Interstitial Cystitis/Bladder Pain Syndrome Based on Gene Expression." J Cell Physiol. 2019;234(8):12301-12308. doi:10.1002/jcp.28009

11. Mohammad A, Laboulaye MA, Shenhar C, Dobberfuhl AD. "Mechanisms of Oxidative Stress in Interstitial Cystitis/Bladder Pain Syndrome." Nat Rev Urol. 2024;21(7):433-449. doi:10.1038/s41585-023-00850-y

12. Janev A, Zupančič D, Veranič P, Kuret T. "Oxidative Stress and Chronic Inflammation as Partners in Crime in Interstitial Cystitis/Bladder Pain Syndrome." J Innate Immun. 2025. doi:10.1159/000546901

13. Lamvu G, Carrillo J, Ouyang C, Rapkin A. "Chronic Pelvic Pain in Women: A Review." JAMA. 2021;325(23):2381-2391. doi:10.1001/jama.2021.2631

14. Oh-Oka H. "Clinical Efficacy of 1-Year Intensive Systematic Dietary Manipulation as Complementary and Alternative Medicine Therapies on Female Patients With Interstitial Cystitis/Bladder Pain Syndrome." Urology. 2017;106:50-54. doi:10.1016/j.urology.2017.02.053

15. Friedlander JI, Shorter B, Moldwin RM. "Diet and Its Role in Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) and Comorbid Conditions." BJU Int. 2012;109(11):1584-91. doi:10.1111/j.1464-410X.2011.10860.x

16. FitzGerald MP, Payne CK, Lukacz ES, et al. "Randomized Multicenter Clinical Trial of Myofascial Physical Therapy in Women With Interstitial Cystitis/Painful Bladder Syndrome and Pelvic Floor Tenderness." J Urol. 2012;187(6):2113-8. doi:10.1016/j.juro.2012.01.123

17. Chermansky CJ, Guirguis MO. "Pharmacologic Management of Interstitial Cystitis/Bladder Pain Syndrome." Urol Clin North Am. 2022;49(2):273-282. doi:10.1016/j.ucl.2022.01.003

18. Di XP, Luo DY, Jin X, et al. "Efficacy and Safety Comparison of Pharmacotherapies for Interstitial Cystitis and Bladder Pain Syndrome: A Systematic Review and Bayesian Network Meta-Analysis." Int Urogynecol J. 2021;32(5):1129-1141. doi:10.1007/s00192-020-04659-w

19. Hall BP, Shiromani S, Vanderbeek BL, et al. "Pentosan Polysulfate Maculopathy: Clinical Considerations, Pathobiology, and Causality." Prog Retin Eye Res. 2025:101400. doi:10.1016/j.preteyeres.2025.101400

20. McGwin G, MacLennan P, Owsley C. "Association Between Pentosan Polysulfate Sodium and Retinal Disorders." JAMA Ophthalmol. 2022;140(1):37-42. doi:10.1001/jamaophthalmol.2021.4778

21. Lindeke-Myers A, Hanif AM, Jain N. "Pentosan Polysulfate Maculopathy." Surv Ophthalmol. 2022;67(1):83-96. doi:10.1016/j.survophthal.2021.05.005

22. Fung AT, Sarraf D, Carrillo JM, et al. "Pentosan Polysulfate Maculopathy Following Subcutaneous Injections for Arthritis." JAMA Ophthalmol. 2025. doi:10.1001/jamaophthalmol.2025.5069

23. Moss NP, Chill HH, Sand PK, et al. "A Prospective, Randomized Trial Comparing Intravesical Dimethyl Sulfoxide (DMSO) to Bupivacaine, Triamcinolone, and Heparin (BTH), for Newly Diagnosed Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS)." Neurourol Urodyn. 2023;42(3):615-622. doi:10.1002/nau.25142

24. Li HR, Shen SH, Gao XS, Peng L, Luo DY. "The Efficacy and Safety of Dimethyl Sulfoxide Into the Bladder for the Treatment of Interstitial Cystitis/Bladder Pain Syndrome: A Systematic Review and Meta-Analysis." Neurourol Urodyn. 2025;44(5):1036-1046. doi:10.1002/nau.70036

25. Wang J, Chen Y, Chen J, Zhang G, Wu P. "Sacral Neuromodulation for Refractory Bladder Pain Syndrome/Interstitial Cystitis: A Global Systematic Review and Meta-Analysis." Sci Rep. 2017;7(1):11031. doi:10.1038/s41598-017-11062-x

26. Rekatsina M, Leoni MLG, Visser-Vandewalle V, et al. "Long-Term Outcomes of Sacral Neuromodulation for Refractory Interstitial Cystitis/Bladder Pain Syndrome: A Retrospective Cohort Study." J Clin Med. 2025;14(11):3647. doi:10.3390/jcm14113647

27. Husein R, Tavakkoli M, Abhari SA, et al. "Sacral Nerve Stimulation and Chronic Bladder Pain: Meta-Analysis." Neuromodulation. 2025. doi:10.1016/j.neurom.2025.09.318

28. Buford K, Peters KM, Riedl C, et al. "Global Consensus on Interstitial Cystitis/Bladder Pain Syndrome: An Update on Therapeutic Treatments." Neurourol Urodyn. 2025. doi:10.1002/nau.70106