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The pathophysiology of the overactive bladder associated with spinal cord injury : Involvement of capsaicin-sensitive primary bladder afferent nerves

Research Project

Project/Area Number 11671545
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionSHINSHU UNIVERSITY, SCHOOL OF MEDICINE

Principal Investigator

IGAWA Yasuhiko  Shinshu Univ.Sch.of Med., Dept.of Urology, Associate Professor, 医学部, 助教授 (40159588)

Co-Investigator(Kenkyū-buntansha) SATOH Tomoya  Shinshu Univ.Sch.of Med., Dept.of Urology, Assistant Professor, 医学部, 助手 (30291272)
SEKI Satoshi  Shinshu Univ.Hosp., Dept.of Urology, Assistant Professor, 医学部・附属病院, 助手 (60293502)
ISHIZUKA Osamu  Shinshu Univ.Hosp., Dept.of Urology, Assistant Professor, 医学部・附属病院, 講師 (20184541)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsspinal cord injury / bladder function / β-adrenoceptors / overactive bladder / capsaicin / afferent nerves / レジニフェラトキシン / β-アドレナリン受容体 / ドーパミン受容体 / 膀胱平滑筋 / ベータ・アドレナリン受容体
Research Abstract

(1) In conscious rats with and without cronic spinal cord injury (SCI), the effect of intravesical instillation of capsaicin or resiniferatoxin (RTX) on volume-induced rhythmic bladder contractions (RBCs). Both capsaicin (0.1 and 1 mM) and RTX (1 and 10 μM ), instilly intravesically, were found to inhibit RBCs in both control and SCI rats. There was no qualitative difference in response to the drugs between the two groups. However, RTX was approximately 100 times more potent than capsaicin^2.
(2) The clinical and urodynamic effects of intravesical instillation of capsaicin (2 mM in 5 patients) or RTX (1 μM in 3 patients) were investigated in 8 patients with overactive bladder associated with chronic spinal cord injury. Both of these two drugs surppress the overactive bladder and improved both reflexic urinary incontinence and symptoms related to autonomic dysreflexia. The beneficial effect emerged more quickly after RTX treatment than after capsaicin, and lasted for at least 3 months after either of the two drugs. No adverse effects was found.
(3) The relaxant response to adrenergic stimulation in the human normal detrusor was found to be mediated mainly through β3-adrenoceptors (β3-ARs)^1. This was true also in neurogenic (both hyper-reflexic and low-compliant) bladders ^3, ^<12>. Selective β3-AR agonists induced bladder relaxation without affecting the cardiovascular system in the ferret ^7 and surppressed bladder overactivity induced by intravesical instillation of prostaglandin E2 in conscious rats ^5 and bladder overactivity in cerebral infarcted rats^4. These results suggest that selective β3-AR agonists may be used for the treatment of overactive bladder.
(4) Cystometric study in conscios rats showed that Dopamine D1 receptors tonically inhibit the micturition reflex and D2 receptors are involved in facilitation of the micturition reflex^<13>.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Igawa,Y. et al.: "Functional and molecular biological evidence for a possible β_3-adrenoceptor in the human detrusor muscle"Brit.J.Pharmacol.. 126. 819-825 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Komiyama,I. et al.: "Effects of intravesical capsaicin and resiniferatoxin on distension-induced bladder contraction in conscious rats with and without chronic spinal cord injury"The Journal of Urology. 161. 314-319 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Igawa,K, et al.: "Functional role of β_3-adrenoceptors in neurogenic detrusors"Neurourology and Urodynamics. 18. 352-353 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaidoh,K, et al: "Effect of selective β_2-and β_3-adrenoceptor agonists on detrusor hyperreflexia in cerebral-infarcted rats."Neurourology and Urodynamics. 19. 410-411 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeda,H., et al: "Effects of β_2-and β_3-adrenoceptor agonists on prostaglandin-E_2-induced bladder hyperactivity and cardiovascular systemic conscious rats."Neurourology and Urodynamics.. 19. 463-464 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mizusawa,H. et al: "A rat model for investigation of bladder dysfunction associated with demyelinating disease resembling multiple sclerosis."Neurourology and Urodynamics. 19. 689-699 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishizuka,O. et al.: "Role of supraspinal technicians for volume-and L-PUPA induced bladder activity in normal conscious rats"Neurourology and Urodynamics. 19,1. 101-109 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeda,H. et al.: "Role of β_3-adrenoceptor in urine storage in the rat: comparison between the selective β_3-adrenoceptor agonist, CL316,43…"The Journal of Pharmacology and Experimental Therapeutics. 293,3. 939-945 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Gu,B.T. et al.: "Role of super spinal tachykinins for micturition in conscious rats with and without bladder outlet obstruction"Naunyn-Schmiedeberg's Arch Pharmacol. 361. 543-548 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeda,H. et al.: "Characterization of β-adrenoceptor subtypes in the ferret uinary bladder in vitro and in vivo"Eur.J.Pharmacol.. 403,. 147-155 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Igawa,Y. et al.: "Relaxant effects of isoproterenol and selective β_3-adrenoceptor agonists on normal, low compliant and hyperreflexic human bladders"The Journal of Urology. 165,1. 240-244 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Seki,S, et al.: "Role of dopamine D_a and D_2 receptors in the micturition reflex in conscious rats."Neurourology and Urodynamics. 20:1. 105-113 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 安田耕作,井川靖彦 他2名: "排尿障害の薬物療法"三輪書店. 206 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] IGAWA,Y., et al.: "Functional and molecular biological evidence for a possible_3-adrenoceptor in the human detrusor muscle"Brit.J.Pharmacol.. 126. 819-825 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] KOMIYAMA,I., et al.: "Effects of intravesical capsacin and resiniferatoxin on destension-induced bladder contraction in conscious rats with and without chronic spinal cord injury"J.Urol.. 161. 314-319 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] IGAWA,Y., et al.: "Functional role of β3-adrenoceptor in neurogenic detrusors."Neurouro. Urodyn. 18. 352-353 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] KAIDOH,H., et al.: "Effects of selective β2-and β3-adrenoceptor agonists on detrusor hyperreflexia in cerebral infarcted rats"Neurouro.Urodyn.. 18. 410-411 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] TAKEDA,H., et al.: "Effects of β2- and β3-adrenoceptor agonists on prostaglandin-E2-induced bladder hyperactivity and cardiovascular system in conscious rats."Neurouro.Urodyn.. 18. 463-464 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] TAKEDA,H., et al.: "Role of β_3-adrenoceptor in urine storage in the rat : Comparison between the selective β_3-adrenoceptor agonist, CL316,243, and various smooth muscle relaxants."J Pharmacol Exp Ther. 293. 939-945 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] TAKEDA,H., et al.: "Characterization of β-adrenoceptor subtypes in the ferret urinary bladder in vitro and in vivo."Eur J Pharmacol. 403. 147-155 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] ISHIZUKA,O, et al.: "Role of supraspinal tachykinins for volume-and L-Dopa-induced bladder activity in normal conscious rats."Neurourol Urodyn. 19. 101-109 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] GU,B.J., et al.: "Role of supraspinal tachykinins for micturition in conscious rats with and without bladder outlet obstruction."Naunyn-Schmiedeberg's Arch Pharmacol. 361. 543-548 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] KIYONO,Y., et al.: "Improvement of urological-management abilities in individuals with tetraplegia by reconstructive hand surgery"Spinal Cord. 38. 541-545 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] MIZUSAWA,H., et al.: "A rat model for investigation of bladder dysfunction associated with demyelinating disease resembling multiple sclerosis."Neurouro Urodyn. 19. 689-699 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] IGAWA,Y., et al.: "Relaxant effects of isoproterenol and selective β_3-adrenoceptor agonists on normal, low compliant, and hyperreflexic human bladders"J Urol. 240-244 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] SEKI,S., et al.: "Role of dopamine D1 and D2 receptors in the micturition reflex in conscious rats."Neurouro Urodyn. 105-113 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishiguka,O. et al.: "Role of supraspinal tachykinins for volume-and L-DOPA induced bladder activity in normal conscious rats"Neuro urology and Urodynamics. 19,1. 101-109 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeda,H. et al.: "Role of β3-adrenoceptor in Urine storage in the rat : Comparison between the selective β3-adrenoceptor agonist,CL316,93…"The Journal of Pharmacology and Experimental Therapeutics. 293,3. 939-945 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Gu,B.J. et al.: "Role of supraspinal tachykinins for micturition in conscious rats with and without baladder outlet obstruction"Nauryn-Schmicdeberg's Arch Pharmacol. 361. 543-548 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeda,H. et al: "Characterization of β-adrenoceptor subtypes in the ferret urinary bladder in vitro and in vivo"Eur.J.Pharmacol.. 403. 147-155 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Igawa,Y. et al.: "Relaxant effects of isoproterenol and selective β_3 -adrenoceptor agonists on normal, low compliant and hyperreflexic human bladders"The Journal of Urology. 165,1. 240-244 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Seki,S, et al.: "Role of dopamine D1 and D2 receptors in the micturition reflex in conscious rats"Neurourlogy and Urodynamics. 20,1. 105-113 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 安田耕作,井川靖彦 他2名: "排尿障害の薬物療法"三輪書店. 206 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] IGAWA,Y.etal.: "Functional role of β_3-adrenoceptors in neurogenic human detrusors"Neurourology and Urodynamics. 18・4. 352-353 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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