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Desensitization of bladder sensory fibers by intravesical capsaicin or capsaicin analogs. A new strategy for treatment of urge incontinence in patients with spinal detrusor hyperreflexia or bladder hypersensitivity disorders

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Abstract

Recent experimental studies have identified a category of unmyelinated type C bladder afferent fibers in the pelvic nerves which are extremely sensitive to capsaicin. Sensory input conveyed by these fibers triggers a spinal reflex which, in chronic spinalized animals, facilitates and controls micturition. In addition, bladder C fibers were also shown to have a role in bladder pain perception. In humans capsaicin-sensitive afferent fibers also innervate the bladder and contribute to the reflexogenic control of the detrusor muscle and to bladder pain perception. Desensitization of such fibers by intravesical administration of capsaicin, presumably by blocking sensory transmission, has been shown to reduce involuntary micturition and to increase bladder capacity in patients with detrusor hyperreflexia of spinal origin, and to reduce the intensity of bladder pain in patients with bladder hypersensitivity. Very recently, resiniferatoxin, an ultrapotent capsaicin analog, was shown to have a similar clinical effect in this subset of patients. However, unlike capsaicin, resiniferatoxin did not evoke acute irritative urinary symptoms during bladder instillation.

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References

  1. Abrams P, Blaivas JG, Stanton SL, Anderson JT. Standardisation of terminology of lower urinary tract dysfunction.Scand J Urol Nephrol 1988;114(Suppl):5–19

    Google Scholar 

  2. Milsom I, Ekelund P, Molander U, Arvidsson L, Areskoug B. The influence of age, parity, oral contraception, hysterectomy and menopause on the prevalence of urinary incontinence in women.J Urol 1993;149:1459–1462

    PubMed  Google Scholar 

  3. Wyman JF. The costs of urinary incontinence.Eur Urol 1997;32(Suppl 2):13–19

    PubMed  Google Scholar 

  4. Ekelund P, Grimby AG, Milson I. Urinary incontinence—social and financial cost high.Br Med J 1993:306:1344

    Google Scholar 

  5. Hu T. Impact of urinary incontinence on health care costs.J Am Geriatr Soc. 1990;38:292–295

    PubMed  Google Scholar 

  6. Diokno AC. Epidemiology of female incontinence. In: Raz SW, ed. Female urology. Philadelphia: WB Saunders, 1996;73–79

    Google Scholar 

  7. Hampel C, Wienhold D, Benken N, Eggersmann C, Thuroff JW. Prevalence and natural history of female incontinence.Eur Urol 1997;32(Suppl 2):3–12

    Google Scholar 

  8. Stephenson TP, Mundy AR. The urge syndrome. In: Mundy AR, Stephenson TP, Wein AJ, eds. Urodynamics. Edinburgh: Churchill Livingstone, 1994:263–275

    Google Scholar 

  9. Heritz DM, Blaivas JG. Evaluation of urinary tract dysfunction. In: Raz SW, ed. Female urology. Philadelphia: WB Saunders, 1996:89–96

    Google Scholar 

  10. Szallasi A, Blumberg PM. Vanilloid receptors: new insights enhance potential as therapeutic target.Pain 1996;68:195–208

    PubMed  Google Scholar 

  11. Walpole CSJ, Bevan S, Bovermann G. et al. The discovery of capsazeprine, the first competitive antagonist of the sensory neuron excitants capsaicin and resiniferatoxin.J Med Chem 1994;37:1942–1954

    PubMed  Google Scholar 

  12. Szallasi A, Blumberg PM. Specific binding of resiniferatoxin, an ultrapotent capsaicin analog by dorsal root ganglion membranes.Brain Res 1990;524:106–111

    PubMed  Google Scholar 

  13. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway.Nature 1997;389:816–824

    PubMed  Google Scholar 

  14. Bevan SJ, Docherty RJ. Cellular mechanisms of the action of capsaicin. In: Wood J, ed. Capsaicin in the study of pain. London: Academic Press. 1993:27–44

    Google Scholar 

  15. Szolcsányi J, Jancsó-Gabor A, Joo F. Functional and fine structural characteristics of the sensory neuron blocking effect of capsaicin.Naunyn Schmiedeberg's Arch 1975;287:157–161

    Google Scholar 

  16. McMahon SB, Lewin G, Bloom SR. The consequences of longterm topical capsaicin application in the rat.Pain 1991;44:301–310

    PubMed  Google Scholar 

  17. de Groat WD. A neurologic basis for the overactive bladder.Urology 1997;50(Suppl 6A):36–52

    PubMed  Google Scholar 

  18. Maggi CA, Barbanti G, Santicioli P et al. Cystometric evidence that capsaicin-sensitive nerves modulate the afferent branch of the micturition reflex in humans.J Urol 1989;142:150–154

    PubMed  Google Scholar 

  19. Blaivas JG. The neurophysiology of micturition: a clinical study of 550 patients.J Urol 1982;127:958–963

    PubMed  Google Scholar 

  20. Fowler CA, Jewkes D, McDonald WI, Lynn B, de Groat WC, Intravesical capsaicin for neurogenic bladder dysfunction.Lancet 1992;339:1239

    Google Scholar 

  21. Fall M, Lindstrom S, Mazières L. A bladder cooling reflex in the cat.J Physiol (Lond) 1990;427:281–300

    Google Scholar 

  22. Geirsson G, Fall M, Sullivan L. Clinical and urodynamic effects of intravesical capsaicin treatment in patients with chronic traumatic spinal detrusor hyperreflexia.J Urol 1995;154:1825–1829

    PubMed  Google Scholar 

  23. Habler HJ, Janig W, Koltzenburg M. Activation of unmyelinated afferent fibers by mechanical stimuli and inflammation of the urinary bladder in the cat.J Physiol (Lond.) 1990;425:545–562

    Google Scholar 

  24. Cruz F, Avelino A, Lima D, Coimbra A. Activation of c-fos protooncogene in the spinal cord following noxious stimulation of the urinary bladder.Somatosens Motor Res 1994;11:319–325

    Google Scholar 

  25. Koltzenburg M. Stability and plasticity of nociceptor function and their relationship to provoked and ongoing pain.Semin Neurosci 1995;7:199–210

    Google Scholar 

  26. Andersson KE. The overactive bladder: pharmacologic basis of drug treatment.Urology 1997;50(Suppl 6A):74–84

    PubMed  Google Scholar 

  27. Appell RA. Clinical efficacy and safety of tolterodine in the treatment of overactive bladder: a pooled analysis.Urology, 1997; 50(Suppl 6A):90–96

    PubMed  Google Scholar 

  28. Burnstock G. The chaning face of autonomic neurotransmission.Acta Physiol Scand 1986;126:67–91

    PubMed  Google Scholar 

  29. Levin RM, Ruggieri MR, Lee W, Wein AJ. Effect of chronic atropine administration on the rat urinary bladder.J Urol 1989;139:1347–1351

    Google Scholar 

  30. Mark SD, Webster GD. Detrusor hyperactivity. In: Raz SW, ed. Female urology. Philadelphia: WB Saunders, 1996;231–243

    Google Scholar 

  31. Zinner NR. The surgical principles associated with voiding dysfunction.Curr Opin Urol 1993;3:290–295

    Google Scholar 

  32. Fowler CA, Beck RO, Gerrard S, Betts CD, Fowler CG. Intravesical capsaicin for treatment of detrusor hyperreflexia.J Neurol Neurosurg Psychiatr 1994;57:169–173

    PubMed  Google Scholar 

  33. Das AS, Chancellor MB, Watanabe T, Sedor J, Rivas DA. Intravesical capsaicin in neurologic impaired patients with detrusor hyperreflexia.J Spinal Cord Med 1996;19:190–193

    PubMed  Google Scholar 

  34. Cruz F, Guimarães M, Silva C, Rio ME, Coimbra A, Reis M. Desensitization of bladder sensory fibers by intravesical capsaicin has long-lasting clinical and urodynamic effects in patients with hyperactive or hypersensitive bladder dysfunction.J Urol 1997;157:585–589

    PubMed  Google Scholar 

  35. De Ridder D, Chandiramani V, Dasgupta P, van Poppel H, Baert L, Fowler CJ. Intravesical capsaicin as a treatment for refractory detrusor hyperreflexia: a dual center study with long-term followup.J Urol 1997;158:2087–2092

    PubMed  Google Scholar 

  36. Cruz F, Avelino A, Coimbra A. Desensitization follows excitation of bladder primary afferents by intravesical capsaicin, as shown by c-fos activation in the rat spinal cord.Pain 1996;64:553–557

    PubMed  Google Scholar 

  37. Barbanti G, Maggi CA, Beneforti P, Baroldi P, Turini D. Relief of pain following intravesical capsaicin in patients with hypersensitive disorders of the lower urinary tract.Br J Urol 1993;71:686–691

    PubMed  Google Scholar 

  38. Lazzeri M, Beneforti P, Benaim G, Maggi CA, Lecci A, Turini D. Intravesical capsaicin for treatment of severe bladder pain: a randomized placebo controlled study.J Urol 1996;156:947–952

    PubMed  Google Scholar 

  39. Graft RM, Porreca F. Tetracaine attenuates irritancy without attenuating desensitization produced by intravesical resiniferatoxin in the rat.Pain 1994;57:351–359

    PubMed  Google Scholar 

  40. Avelino A, Cruz F, Coimbra A. Lidocaine prevents noxious excitation of bladder afferents induced by intravesical capsaicin without interfering with the ensuing sensory desensitization. An experimental study in the rat.J Urol 1998;159:567–570

    PubMed  Google Scholar 

  41. Chandiramani VA, Peterson T, Duthie GS, Fowler CJ. Urodynamic changes during intravesical instillations of capsaicin.Br J Urol 1996;77:792–797

    PubMed  Google Scholar 

  42. Dasgupta P, Chandiramini V, Parkinson MC, Beckett A, Fowler CJ. Treating the human bladder with capsaicin: is it safe?Eur Urol 1998;33:28–31

    Google Scholar 

  43. Cruz F, Avelino A, Coimbra A. Intravesical resiniferatoxin desensitizes bladder sensory fibers in a dose dependent manner.J Urol 1997;157 (Suppl):79

    PubMed  Google Scholar 

  44. Cruz F, Guimarães M, Silva C, Reis M. Intravesical resiniferatoxin, a capsaicin analog, represses bladder hyperreflexia without evoking significant acute discomfort.Lancet 1997; 350:640–641

    Google Scholar 

  45. Lazzeri M, Beneforti P, Turini D. Urodynamic effects of intravesical resiniferatoxin in humans: preliminary results in stable and unstable detrusor.J Urol 1997;158:2093–2096

    PubMed  Google Scholar 

  46. Brading AF. A myogenic basis for the overactive bladder.Urology 1997;50(Suppl 6A):57–67

    PubMed  Google Scholar 

  47. Steers WD, de Groat WC: Effect of bladder outlet obstruction on micturition reflex pathways in the rat.J Urol 1988;140:864–871

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, Hospital de São João, 4200, Porto, Portugal

    F. Cruz

  2. Faculty of Medicine of Oporto, Institute of Histology and Embryology, Oporto, Portugal

    F. Cruz

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  1. F. Cruz
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Cruz, F. Desensitization of bladder sensory fibers by intravesical capsaicin or capsaicin analogs. A new strategy for treatment of urge incontinence in patients with spinal detrusor hyperreflexia or bladder hypersensitivity disorders. Int Urogynecol J 9, 214–220 (1998). https://doi.org/10.1007/BF01901607

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