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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]

For the procedural and surgical end of the pathway, see Pelvic Floor Physical Therapy, Intradetrusor onabotulinumtoxinA, Sacral Neuromodulation, and the major-surgery options (Bladder Augmentation, Supratrigonal Cystectomy, Simple Cystectomy + Urinary Diversion).

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 responseLesion-directed fulguration/triamcinolone; selected refractory cases may be considered for cyclosporineVariable; multimodal

Epidemiology​

Prevalence:[1][7][8]

  • Women: 2.7–6.5% using symptom-survey definitions; 1.08% in a US population estimate derived from chart-validated Veterans Health Administration data and demographic adjustment
  • Men: 0.66% in the same chart-validated, demographically adjusted estimate
  • 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 women meeting survey symptom criteria reported an IC/BPS diagnosis; survey-positive symptoms and a clinically established diagnosis are not interchangeable

Demographics:[1][9]

  • Sex ratios vary substantially with case definition and ascertainment; a universal 10:1 ratio is not supported by the chart-validated estimates above
  • 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)
  • Individualized dietary modification based on reproducible symptom triggers
  • 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​

Commonly reported triggers include coffee, citrus, tomatoes, alcohol, carbonated drinks and spicy foods. Use a symptom diary and elimination/rechallenge to identify personal triggers; blanket exclusion of all these foods or all potassium-rich foods is not required.[3][14][15]

Evidence for supplements such as calcium glycerophosphate is limited. Sodium bicarbonate adds sodium and alkali exposure and is not a routine treatment for every patient.[15]

A small dietary-intervention study reported improved symptom and pain scores; this does not establish one effective exclusion diet for all IC/BPS phenotypes.[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: in 81 women with pelvic floor tenderness and symptoms for no more than three years, 10 sessions of myofascial PT produced 59% vs 26% global response with massage (p = 0.0012). Pain, urgency and frequency improved in both groups without significant between-group differences in those individual secondary outcomes.[16]

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]

CUA 2025 changes the PPS discussion: it conditionally recommends against oral PPS, weighing limited benefit against visual harm and cost. It makes no recommendation for or against cyclosporine because evidence is insufficient, including for differential benefit by Hunner status.[29] For current doses, drug monitoring and reassessment, use the oral IC/BPS pharmacology hub.

AgentMechanismDosingEvidenceKey considerations
AmitriptylineTCA; anticholinergic, antihistamine, analgesicSee pharmacology hubBICSI reduction; anticholinergic side effects
Pentosan polysulfate (PPS)Proposed barrier protectionSee pharmacology hubAUA option; CUA2025 conditional againstFDA-approved oral agent; retinal risk can be irreversible
HydroxyzineH1 antihistamineSee pharmacology hubCSedation, anticholinergic burden and QT risk
CimetidineH2 blockerSee pharmacology hubBLimited evidence; may reduce pain
Cyclosporine ACalcineurin inhibitorSpecialist-directedOff-labelSelected refractory cases; nephrotoxicity and monitoring burden

Older network meta-analysis rankings do not establish a best oral agent.[18] AUA permits cyclosporine, particularly for Hunner lesions refractory to fulguration and/or triamcinolone; this is an option requiring individualized toxicity assessment, not a general efficacy hierarchy.[3]

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)

US prescribing-information warning (not boxed) and screening:[30]

  • Detailed ophthalmologic history before initiation
  • Comprehensive retinal examination before starting in patients with preexisting eye disease
  • Baseline retinal exam including OCT and fundus autofluorescence is suggested for all patients within 6 months of starting
  • Periodic retinal exams during treatment; no single annual interval is specified in the label
  • If pigmentary changes develop, reevaluate continuation and maintain retinal follow-up after stopping because changes may progress

Intravesical Instillations​

AUA 2022 (Option; evidence Grade B or C depending on agent): DMSO, heparin, and/or lidocaine may be administered.[3]

AgentMechanismProtocolEvidenceNotes
DMSO 50% w/w (Rimso-50)Multimodal local effectsLabel: 50 mL, 15-minute dwell, every 2 weeks until maximal relief, then longer intervalsGrade CFDA-approved intravesical agent; garlic odor[31]
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

A 2025 DMSO meta-analysis included both randomized and observational evidence.[24] Separately, Moss 2023 compared DMSO plus triamcinolone with BTH (bupivacaine/triamcinolone/heparin), not DMSO alone. Of 83 randomized patients, 70 completed treatment; the primary responder comparison among patients with evaluable paired ICSI data was nonsignificant (63% vs43%, p=0.15), while pain and nocturia changes favored DMSO plus triamcinolone.[23]

No single intravesical agent or cocktail is preferred by CUA 2025.[29] Use a pharmacy-validated formulation; see the intravesical pharmacology hub for the exact Moss study mixtures and evidence limitations.

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 symptom flares can occur. Observational repeat-treatment studies are reassuring about capacity, but do not guarantee absence of harm. Avoid high-pressure, long-duration hydrodistension because of bladder rupture and sepsis risk.

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

When Hunner lesions are identified:

  • Fulguration with electrocautery
  • Intralesional triamcinolone, with concentration, aliquots and total dose determined by the specialist protocol; see intralesional corticosteroids
  • Combination

Benefit often lasts months and recurrence may require retreatment. Follow symptoms and bladder capacity over time; repeated ablation should not be presented as risk-free or guaranteed to preserve capacity.

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

An off-label option for IC/BPS after inadequate improvement with other treatments. CUA 2025 gives botulinum toxin A, with or without hydrodistension, a conditional recommendation based on very low-certainty evidence; it is not uniquely supported by strong evidence.[29] Benefit may last 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.

Evidence: a meta-analysis of 583 patients reported improved pain, but predominantly uncontrolled, heterogeneous studies limit causal inference. Longer-term cohorts report sustained improvement in selected recipients; these data do not establish a predictable durable response for all refractory patients.[25][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 cystectomy with augmentationReservoir reconstructed; trigone preservedVariable; careful bladder-centric selection
Urinary diversion ± cystectomyDivertsMay or may not eliminate pain

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

Emerging Therapies​

Investigational approaches reported in the literature; inclusion does not imply regulatory approval or an ongoing trial:[1][28]

TherapyMechanismStatus
Certolizumab pegolAnti-TNF monoclonal antibodyInvestigational; limited trial evidence
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; the options below are not a mandatory sequence:[3]

  • All patients — education, self-care, behavioral modifications
  • Pelvic floor tenderness — manual physical therapy (avoid Kegels)
  • Suspected Hunner lesions — cystoscopy → fulguration and/or triamcinolone if present
  • Oral medications — symptom-directed options; PPS requires the updated guideline/retinal-risk discussion above
  • Intravesical — DMSO, heparin, and/or lidocaine (alone or in combination)
  • Procedures — hydrodistension, botulinum toxin A, sacral neuromodulation
  • Major surgery — augmentation cystoplasty, supratrigonal cystectomy, simple cystectomy + urinary diversion (carefully selected bladder-centric disease or an end-stage small fibrotic bladder after other feasible treatments have failed; Hunner lesions are not required).[3]

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

29. Doiron RC, Tadayon B, Violette PD, et al. "2025 Canadian Urological Association Guideline: Selected treatment recommendations for interstitial cystitis/bladder pain syndrome." Can Urol Assoc J. 2025;19(4):90–103. doi:10.5489/cuaj.9182

30. Janssen. ELMIRON US prescribing information. Revised July 2024; accessed September 11, 2026.

31. RIMSO-50 US prescribing information. Updated March 17, 2021; accessed September 11, 2026.