BLADDER PAIN SYNDROME (BPS)
Semir A. S. Al Samarrai
Interstitial cystitis (IC) describes a chronic, distressing bladder condition (2)
The so called ulcer, which is a typical cystoscopic finding in 10-50% of IC patients, was decribed by Amy Hunner at the beginning of the last century (3, 4).
Subsequent research (5,7) has shown that IC encompassed a heterogeneous spectrum of disorders; with different endoscopic and histopathological presentations, with inflammation an important feature in only a subset of patients.
To embrace all patients suffering from bladder pain, the term Painful Bladder Syndrome (PBS) or BPS have suggested as more accurate when referring to pain in the bladder region, while assuming IC with Hunner’s lesion as a specific type of chronic inflammation of the bladder (8, 9).
Bladder pain syndrome should be diagnosed on the basis of pain, pressure or discomfort associated with the urinary bladder, accompanied by at least one other symotoms, such as daytime and /or night time increase urinary frequency, the exclusion of confusable diseases as the cause of symptoms, and if indicated, cystoscopy with hydrodistension and biopsy (9).
Reports of the prevalence of BPS have varicel greatly, along with the diagnosis criteria and populations studied. Recent report generally showed higher figures than earlier ones, ranging from 0.06% to 30% (10, 11, 12, 13, 14, 15, 16, 17, 18, 19).
There is a female predominance of about 10:1 (4, 71, 81, 82). Evidence that BPS may have a genetic component has been presented in several studies, but may contribute to less than one third of total variation in susceptibility for BPS, with the remainder being environmental (20, 21, 22, 23).
Pain is often a dominant symptom, therefore, many patients try commonly used analgesics at some stages of the disease. However, pain relief is disappointing because the visceral pain experienced in BPS responds poorly to analgesic drugs.
Short-term opoids may be indicated for breakthrough or exacerbated pain and periodic flare-ups. Long-term opoids may be considered after all other available therapeutic options have been excluded (24).
Reports an outcome with corticosteroid therapy have been both promising (25) and discouraging (26). Soucy et al (27) have suggested a trial of Prednisone ((25mg daily for 1-2 months, afterwards reduced to the minimum required for symptom relief)) in patients with severe ulcerative BPS.
Mast cells may play a role in BPS. Histamine is one of the substances released by mast cells. Histamine receptor antagonist have been to block the H1 (28) as well as the H2(29) receptor subtypes, with variable results. The tricyclic antidepressant (Amitriptyline) has alleviated symptoms in BPS, probably via mechanisms such as blockade of acetylcholine receptors, inhibition of recaptake of released Serotonin and noradrenalin, and blockade of histamine H1 receptors.
4) Pentosan-Poly-Sulphate-Sodium has been evaluated in double-blind, placebo-controlled studies. This agent positive effect by the BPS is thought to substitute for a defect in the GAG layer. Subjective improvement of pain, urgency, frequency, but not nocturia, has been reported in patients taking the drug compared to placebo (30, 31).
5) Antibiotics have a limited role in the treatment of BPS. Antibiotics alone or in combination may be associated with decreased symptoms in some patients, but do not represent a major advance in therapy for BPS (32).
6) Immunosuppressants (such as Azathioprine, Cyclosporine and methotrexat were initially evaluated in open studies with good effect on pain, but a limited effect on urgency and frequency (23,24). Men recent studies of Cyclosporin A have reported promising results, daily voiding maximal bladder capacity and voided volume was significantly improved after one year of treatment (35).
7) Ouercetin: is a bioflavonoid that maybe effective in male pelvic pain syndrome (36).
Intravesical application of medications establishes high concentration at the target, with few systemic side effects.
Hyaluronic acid: is a natural proteoglycan aimed at repairing defects in the urothelial gluosaminoglycan (GAG) layer. A response rate of 56% at week 4 and 71% at week 7 was reported in patients treated with hyaluvonic acid. (37).
Chondroitin-sulphate: Intravesical Chondroitin-sulphate (38), demonstrated beneficial effect in patients with a positive potassium stimulation test.
Bacillus Calmette Guerin (BCG)
The Turberculosis BCG vaccine is used for immunomodalatory properties in the Transvesical treatment of superficial bladder carcinoma, but because of the low response rate of 18% for BCG in BPS patients, the argument against routine use of BCG for BPS has been substanciated (39).
a) Bladder distension is a common treatment for BPS scientific justification is scarce.
b) Tranurethral Resection (TUR), coagulation and laser. Endourological ablation of blade tissue aims to eliminate urothelial, mostly Hunner lesions (21).
Transurethral application of the (Nd-YAG) Laser is suggested as an alternative to TUR for endogenic treatment in BPS (40).
Controlled studies are still lacking Endorological resection is not applicable to non-ulcer BPS.
c) Botulinum toxin (BTX-A) may have an antinoceptive effect on bladder afferent pathways, producing both sympathomatic and urodynamic improvements (41). Trigonal-only injection seem effective and long-lasting because of 87% of patients reported improvement after 3 month follow-up period in a study by Pinto et al. (42).
Sacral Nerve Stimulation (SNS) or Pudendal Nerve Stimulation (PNS) (43).
Sacral neuromodulation showed adequate improvement for the symptoms of refractory BPS Reoperation rate was 25% (44).
1) Behavioural bladder training techniques are attractive for BPS patients with predominant symptoms of frequency/urgency but hardly any pains (45).
2) Diet. In analysis of the Interstitial Cystitis Data Base (ICDB) cohort study special diets were among the five most commonly used therapies (46). Bade et al. (47) have found that BPS patients consume significantly fewer calories, less fat and coffee, but more fiber. Scientific data on a rationale for such diets are unavailable. The concentration of some metabolity and amino acids appears to be changed in BPS (48).
Overall, dietary management is a common-self care strategy in BPS and after a cost-effective therapeutic approach.
Comprehensive instructions on how to identify individual trigger foods are given in the IC-Network. Patient Handbook. However, scientific data are limited and dietary restriction alone does not produce complete symptomatic relief.
3) Acupuncture: In non-curable and agonising diseases like BPS, desperate patients often try complementary medicines, such as acupuncture. However, scientific evidence for such treatments is often poor, with contradictory results from few low evidence reports on acupuncture, with any effects appearing to be limited and temporary. (49).
4) Hypnosis: is a therapeutic adjunct in the management of cancer, surgical disease and chronic pain. Although used in urological patients (50, 51), there are no scientific data on its effect on BPS symptoms.
5) Physiotherapy: General body exercises may be beneficial in some BPS patients(52)
When all efforts fail to relieve disabling symptom, surgical removal of the diseased bladder is the ultimate option (53, 54, 55, 56).
Three major techniques of bladder resection are common
- Supratrigonal (i.e. trigone-sparing) Cystectomy
- Subtrigonal Cystectomy
- Radical Cystectomy including excision of the urethra
1. D. Engeler, Baranowski A.P., et al. Guidelines on Chronic Pelvic Pain: 1-132.2012.
2. Skene AJC. Disease of the bladder and urethra in women. New York: William Wood 1887; 167.
3. Hunner GL. A rare type of bladder ulcer in women: report of cases. Boston Med Surg J 1915;172:660-4.
4. Hunner G. Elusive ulcer of the bladder: further notes on a rare type of bladder ulcer with report of 25 cases. Am J Obstet 1918;78:374-95.
5. Hand JR. Interstitial cystitis: report of 223 cases (204 women and 19 men). J Urol. 1949 Feb;61(2):291-310.
6. Messing EM, Stamey TA. Interstitial cystitis: early diagnosis, pathology, and treatment. Urology 1978 Oct;12(4):381-92.
7. Fall M, Johansson SL, Aldenborg F. Chronic interstitial cystitis: a heterogeneous syndrome. J Urol 1987 Jan;137(1):35-8.
8. Abrams P, Cardozo L, Fall M, et al. The standardization of terminology of lower urinary tract function: report from the Standardisation of the International Continence Society. Am J Obstet Gynecol 2002 Jul:187(1):116-26.
9. Van de Merwe JP, Nordling J, Bouchelouche P, et al. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol 2008 Jan;53(1):60-7.
10. Oravisto KJ. Epidemiology of interstitial cystitis. Ann Chir Gynaecol Fenn 1975;64(2):75-7.
11. Held PJ, Hanno PM, Wein Aj. In: Hanno PM, Staskin DR, Krane RJ, Wein AJ, eds. Interstitial Cystitis. Epidemiology of interstitial cystitis. London: Springer Verlag, 1990, pp. 29-48.
12. Bade JJ, Rijcken B, Mensink HJ. Interstitial cystitis in The Netherlands: prevalence, diagnostic criteria and therapeutic preferences. J Urol 1995 Dec;154(6):2035-7; discussion 2037-8.
13. Jones CA, Harris MA, Nyberg L. Prevalence of interstitial cystitisin the United States, Proc Am Urol Ass J Urol 1994;151 (Suppl):423A.
14. Curhan GC, Speizer FE, Hunter DJ, et al. Epidemiology of interstitial cystitis: a population based study. J Urol 1999 Feb;161(2):549-52.
15. Leppilahti m, Sairanen J, Tammela TL, et al. Finnish Interstitial Cystitis-Pelvic Pain Syndrome Study Group. Prevalence of clinically confirmed interstitial cystitis in women: a population based study in Finland. J Urol 2005 Aug; 174(2):581-3.
16. Temml C, WehrbergerC, Reidl C, et al. Prevalence and correlates for interstitial cystitis symptoms in women participating in a health screening project. Eur Urol. 2007 mar; 51(3):803-8;discussion 809.
17. Burkman RT. Chronic pelvic pain of bladder origin: epidemiology, pathogenesis and quality of life.
18. Roberts RO, Bergstralh EJ, Bass SE, et al. Incidence of physician-diagnosed interstitial cystitis in Olmsted Country: a community-based study. BJU Int 2003 Feb;91(3):181-5.
19. Parsons CL, Tatsis V. Prevalence of Interstitial cystitis in young women. Urology. 2004 Nov;64(5):866-70.
20. Greenberg E, Barnes R, Stewart S, et al. Transurethral resection of Hunner’s ulcer. J Urol 1974 jun;111(6):764-6.
21. Koziol Ja. Epidemiology of Interstitial cystitis. Urol Clin North Am 1994 Feb; 21(1):7-20.
22. Parsons CL, Zupkas P, Parsons JK. Intravesical potassium sensitivity in patients with interstitial cystitis and urethral syndrome. Urology 2001 Mar;57(3):428-32; discussion 432-3.
23. Altman D, Lundholm C, Milsom I, et al. The genetic and environmental contribution to the occurrence of bladder pain syndrome: an empirical approach in a nationwide population sample. Eur Urol. 2011. Feb;59(2):280-5.
24. Nickel JC. Opioids for chronic prostatitis and interstitial cystitis: lesons learned from th 11th world Congress on Pain. Urology 2006 Oct;68(4):697-701.
25. Badenoch AW. Chronic interstitial cystitis. Br J Urol 1971 Dec;43(6):718-21.
26. Pool TL. Interstitial cystitis: clinical considerations and treatment. Clin Obstet Gynecol 1967 Mar;10(1):185-91.
27. Soucy F, Grégoire m. Efficacy of prednisone for severe refractory ulcerative interstitial cystitis. J Urol 2005 Mar;173(3):841-3; discussion 843.
28. Theoharides TC. Hydroxyzine in the treatment of interstitial cystitis. Urol Clin North Am 1994 Feb;21(1):113-9.
29. Sesshadri P, Emerson L, Morales A. Cimetidine in the treatment of interstitial cystitis. Urology 1994 Oct;44(4):614-6.
30. Mulholland SG, Hanno p, Parsons CL, et al. Pentosan Polysulfate sodium for therapy of interstitial cystitis. A double-blind placebo-controlled clinical study. Urology 1990 Jun:35(6):552-8.
31. Hwang P, Auclair B, Beechinor D, et al. Efficacy of pentosan polysulfate in the treatment of interstitial cystitis: a meta-analysis. Urology 1997 Jul;50(1):39-43.
32. Warren JW, Horne LM, Hebel JR, et al. Pilot study of sequential oral antibiotics for the treatment of interstitial cystitis. J Urol 2000 Jun; 163(6):1685-8.
33. Oravisto KJ, Althan OS. Treatment of interstitial cystitis with immunosuppression and chloroquine derivatives. Eur Urol 1976;2(2):82-4.
34. Forsell T, Ruutu M, Isoniemi H, et al. Cyclosporine in severe interstitial cystitis. J Urol 1996 May; 155(5):1951-3.
35. Sairanen J, Tammela TL, Leppilahti M, et al. cyclosporine A and pentosan polysulfate sodium for the treatment of interstitial cystitis: a randomized comparative study. J Urol 2005 Dec;174(6):2235-8.
36. Katske F, Shokes DA, Sender M, et al. Treatment of interstitial cystitis with quercetin supplement. Tech Urol 2001 Mar; 7(1):44-6.
37. Morales A, Emerson L, Nickel JC, et al. Intravesical hyaluronic acid in the treatment of refractory interstitial cystitis.
38. Palylyk-Colwell E. Chondrointin sulfate for interstitial cystitis. Issues Health Technol 2006 May (84); 1-4.
39. Propert KJ, Mayer R, Nickel JC, et al. Interstitial Cystitis Clinical Trials Group. Followup of patients with interstitial cystitis responsive to treatment with intravesical.
40. Shanberg AM, et al: Treatment of interstitial Cystitis with Neodymium-YAG Laser. J Urol 1985. Nov; 134 (5): 885-8.
41. Smith CP. Et al. Botulinum Toxin-A has antinociceptive effects in treating interstitial cystitis. Urology 2004 Nov, 64 (5) 871-5.
42. Pinto R. et al. Trigonal Injection of Botulinum toxin A in patients with refractor bladder pain syndrome/interstitial cystitis. Eur Urol. 2010 Sep; 58 (3): 360-5.
43. Peters KM, et al; A prospective, single-blind, randomized crossover trial of sacral vs pudental nerve stimulation for interstitial cystitis BJU Int. 2007 Oct; 100 (4): 835-9.
44. Marinkovic SP, et al: Minimum 6 years outcomes for interstitial cystitis treated with sacral neuromodulation Int Urogynecol J Pelvic Floor Dysfunct. 2011 Apr; 22 (4): 407-12.
45. Parsons CL, Koprowski PF. Interstitial Cystitis: successful management by increasing urinary voiding interals. Urology 1991 Mar; 37 (3): 207-12.
46. Rovner E, Propert KJ, Brensinger C, et al. Treatments used in women with interstitial cystitis: The interstitial Cystitis Data Base Study Group. Urology 2000 Dec;56 (6): 940-5.
47. Bade JJ, Peeters JM, Mensink HJ. Is the diet of patients with interstitial cystitis related to their disease? Eur Urol 1997; 32 (2): 179-83.
48. Gillespie L. Metabolic appraisal of the effects of dietary modification on hypertensive bladder symptoms. Br J Urol 1993 Sep; 72 (3):293-7.
49. Chang PL, WU CJ, Huang MH. Long-term outcome of acupuncture in women with frequency, urgency and dysuria. Am J Chin Med 1993;21 (3-4):231-6.
50. Lynch DF Jr. Empowering the patient: hypnosis in the management of cancer, surgical disease and chronic pain. Am J Clin Hypn 1999. Oct;42 (2):122-30.
51. Barber J. Incorporating hypnosis in the management of chronic pain. In: Barber J, Adrian C, eds. Psychological Approaches in the Management of Pain. New York: Brunner/Mazel, 1982; pp. 60-83.
52. Karper WB. Exercise effects on interstitial cystitis: two case reports. Urol Nurs 2004 Jun;24 (3):202-4.
53. Van Ophoven A, Oberpenning F, Hertle L. Long-term results of trigone-preserving orthotopic substitution enterocystoplasty for interstitial cystitis. J Urol 2002 Feb;167(2 Pt 1):603-7.
54. Loch A, Stein U. [Interstitial cystitis. New aspects in diagnosis and therapy]. Urologe A 2004 Sep;43(9):1135-46.
55. Oberpenning F, van Ophoven A, Hertle L. [Chronic Interstitial cystitis] Deutsches Ärzblatt 2002,99: 204-8. [article in German].
56. Oberpenning F, van Ophoven A, Hertle L. Interstitial cystitis: an update. Curr Opin Urol 2002 Jul;12(4): 321-32.
Correspondence:Prof. Dr. SEMIR AHMED SALIM AL SAMARRAI
Professor Doctor of Medicine-Urosurgery, Andrology, and Male Infertility
Dubai Healthcare City, Dubai, United Arab Emirates.
Mailing Address: Dubai Healthcare City, Bldg. No. 64, Al Razi building, Block D,
2nd floor, Dubai, United Arab Emirates, PO box 13576