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Prolonged Modulation of the Micturition Reflex by Electrical Stimulation
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
1999 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Intravesical electrical stimulation (IVES) has been used in treatment of patients with urinary bladder dysfunctions for more than four decades. While some investigators have reported excellent results others have observed less convincing effects or outright failures. The discrepancies may reflect differences in patient selection or stimulation procedure. A better theoretical understanding of the IVES working mechanism might help to improve the success rate of the treatment. The aims of the present study were to provide such information.

Experiments were performed on adult female cats and rats under /alpha/-chloralose anesthesia. IVES was delivered by a catheter electrode in the bladder. At proper intensity and frequency, IVES evoked reflex detrusor contractions that were abolished by bilateral rhizotomy of sacral dorsal roots. Stimulation parameters and response characteristics revealed that bladder mechanoreceptor A/delta/ afferents were activated by the IVES, the same afferents that drive the normal micturition reflex.

Five minutes of continues IVES at 20 Hz induced a prolonged, significant decrease in the micturition threshold volume of anesthetized rats. Similarly, selective bladder A/delta/ afferent stimulation induced a long-lasting enhancement of micturition reflex discharges in cats. A comparable prolonged inhibitory effect on the micturition reflex was demonstrated after ano-genital afferent stimulation. Both modulatory effects occurred without changes in response sensitivity of stimulated afferents. The IVES induced modulation was prevented by transient exposure of the bladder to a local anesthetic and by systemic administration of a glutamate NMDA receptor antagonist.

In conclusion, IVES induces a prolonged modulation of the micturition reflex by an LTP like enhancement of excitatory synaptic transmission in the central micturition reflex pathway. The findings provide an experimental explanation for the neuronal mechanisms underlying the curative effect of IVES in patients with bladder evacuation problems.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 1999. , 50 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 582
Keyword [en]
Intravesical electrical stimulation, IVES, bladder evacuation problems, bladder, micturition reflex
National Category
Urology and Nephrology
Identifiers
URN: urn:nbn:se:liu:diva-4989ISBN: 91-7219-326-3 (print)OAI: oai:DiVA.org:liu-4989DiVA: diva2:20881
Public defence
1999-02-12, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Note
On the day of the public defence the status of article V was: Accepted.Available from: 1999-02-25 Created: 1999-02-25 Last updated: 2012-01-24Bibliographically approved
List of papers
1. Intravesical electrical stimulation: an experimental analysis of the mechanism of action
Open this publication in new window or tab >>Intravesical electrical stimulation: an experimental analysis of the mechanism of action
1992 (English)In: Journal of Urology, ISSN 0022-5347, Vol. 148, no 3, 920-924 p.Article in journal (Refereed) Published
Abstract [en]

The working mechanism of intravesical electrical stimulation (IVES) was evaluated in alpha-chloralose anaesthetized cats and rats. IVES involved a direct activation of bladder mechanoreceptor afferents of the A delta type and as a consequence a central reflex activation of the detrusor. The detrusor response was abolished by bilateral transection of the S1-S3 dorsal roots and by intravesical instillation of lidocaine. The optimal stimulation frequency was 20 Hz. The results offer a theoretical rationale for the use of IVES as treatment of weak detrusor contractility in man.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13504 (URN)
Available from: 1999-02-25 Created: 1999-02-25
2. Intravesical electrical stimulation induces a prolonged decrease in micturition threshold volume in the rat
Open this publication in new window or tab >>Intravesical electrical stimulation induces a prolonged decrease in micturition threshold volume in the rat
1996 (English)In: Journal of Urology, ISSN 0022-5347, Vol. 155, no 4, 1477-1481 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: Intravesical electrical stimulation (IVES) has been used clinically to treat patients with voiding disorders. The aim of the present experimental study was to obtain objective evidence of a modulation of the micturition reflex by intravesical electrical stimulation (IVES).

Materials and Methods: Forty-one female rats, anesthetized by alpha-chloralose were used for the experiments. Intravesical electrical stimulation was given by a catheter electrode in the bladder (5 minutes of continuous stimulation at 20 Hz, 7 to 11 mA). The effect was evaluated by the change in cystometric micturition threshold volume.

Results: The threshold volume of the micturition reflex decreased significantly to 82% of controls after IVES (p<0.001; n=31). The effect was reversible and lasted for about 1 hour. The decrease was prevented by a transient blockade of the bladder nerves during IVES.

Conclusions: Intravesical electrical stimulation induced a prolonged modulation of the micturition reflex in anesthetized rats. The effect was due to activation of bladder mechanoreceptor afferents and remained long after the period of stimulation. It is proposed that the modulation was due to a prolonged enhancement of excitatory synaptic transmission in the central micturition reflex pathway. Such a modulation may underlie the curative effect of IVES in certain voiding disorders.

Keyword
stimulation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13505 (URN)10.1016/S0022-53470166310-9 (DOI)
Available from: 1999-02-25 Created: 1999-02-25 Last updated: 2009-05-20
3. Modulation of the micturition reflex pathway by intravesical electrical stimulation: An experimental study in the rat
Open this publication in new window or tab >>Modulation of the micturition reflex pathway by intravesical electrical stimulation: An experimental study in the rat
1998 (English)In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 17, no 5, 543-554 p.Article in journal (Refereed) Published
Abstract [en]

Intravesical electrical stimulation (IVES) is used clinically to improve bladder evacuation in patients with inadequate micturition contractions. The procedure involves field stimulation of A bladder mechanoreceptor afferents resulting in a prolonged enhancement of the micturition reflex. The aim of the present experimental study in the rat was to identify the site for this neuromodulation, whether it was due to sensitization of bladder mechanoreceptors, to enhancement of transmission in the central micturition reflex pathway, or to improved effectiveness of the peripheral motor system of the bladder. The experiments were performed on female rats, anesthetized by -chloralose. Multi-unit afferent or efferent activity was recorded from bladder pelvic nerve branches during repeated cystometries before and after IVES. The specific antagonist CPPene was used to block central glutaminergic receptors of NMDA type. Micturition threshold volume decreased significantly after IVES. The afferent threshold volume, peak response, and pressure sensitivity were unchanged as were the peak efferent activity and bladder contractility. There was no efferent activity until just before the micturition contraction. The IVES-induced decrease in micturition threshold was blocked by prior administration of the NMDA (N-methyl-D-aspartic acid) antagonist CPPene (3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid). The findings indicate that the IVES-induced modulation of the micturition reflex is due to an enhanced excitatory synaptic transmission in the central micturition reflex pathway. The observed modulation may account for the clinical beneficial effect of IVES treatment.

Keyword
urinary bladder, electric stimulation, neuromodulation, bladder afferent, bladder efferent, micturition reflex, NMDA antagonist, rat
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13506 (URN)10.1002/(SICI)1520-6777(1998)17:5<543::AID-NAU11>3.0.CO;2-G (DOI)
Available from: 1999-02-25 Created: 1999-02-25 Last updated: 2017-12-13Bibliographically approved
4. Optimal conditions for the long-term modulation of the micturition reflex by intravesical electrical stimulation: an experimental study in the rat
Open this publication in new window or tab >>Optimal conditions for the long-term modulation of the micturition reflex by intravesical electrical stimulation: an experimental study in the rat
1999 (English)In: BJU International, ISSN 1464-4096, Vol. 83, no 4, 483-487 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To determine whether induced bladder contractions influence the modulation by intravesical electrical stimulation (IVES) of the micturition reflex in anaesthetized rats, and to identify the optimal IVES frequency and duration.

MATERIALS AND METHODS: Seventy-six adult female rats, anaesthetized by alpha-chloralose. were divided into four groups to study the effect of: (i) IVES in combination with bladder contractions; (ii) bladder contractions alone; (iii) IVES frequency; and (iv) IVES duration. IVES was administered using a catheter electrode in the bladder. The effect of various IVES procedures was evaluated by determining the micturition threshold volume obtained from repeated cystometries before and after stimulation.

RESULTS: Administering IVES with standard parameters induced a significant decrease in the micturition threshold volume for about an hour. There was no difference in outcome between IVES with the bladder filled and contracting during the stimulation or empty and not contracting. Imposed bladder contractions per se had no effect on the micturition threshold volume. IVES at low frequencies (< or = 20 Hz) had a better modulatory effect than higher frequencies and the optimum duration of IVES was 5 min.

CONCLUSIONS: Evoked bladder contractions did not improve the IVES-induced modulation of the micturition reflex. These findings might help to improve the clinical application of the IVES procedure.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13507 (URN)
Available from: 1999-02-25 Created: 1999-02-25 Last updated: 2009-05-20
5. Prolonged increase in micturition threshold volume by anogenital afferent stimulation in the rat
Open this publication in new window or tab >>Prolonged increase in micturition threshold volume by anogenital afferent stimulation in the rat
1998 (English)In: British Journal of Urology International, ISSN 1464-4096, Vol. 82, no 3, 483-487 p.Article in journal (Refereed) Published
Abstract [en]

Objective

To determine whether induced bladder contractions influence the modulation by intravesical electrical stimulation (IVES) of the micturition reflex in anaesthetized rats, and to identify the optimal IVES frequency and duration.

Materials and methods

Seventy-six adult female rats, anaesthetized by α-chloralose, were divided into four groups to study the effect of: (i) IVES in combination with bladder contractions; (ii) bladder contractions alone; (iii) IVES frequency; and (iv) IVES duration. IVES was administered using a catheter electrode in the bladder. The effect of various IVES procedures was evaluated by determining the micturition threshold volume obtained from repeated cystometries before and after stimulation.

Results

Administering IVES with standard parameters induced a significant decrease in the micturition threshold volume for about an hour. There was no difference in outcome between IVES with the bladder filled and contracting during the stimulation or empty and not contracting. Imposed bladder contractions per se had no effect on the micturition threshold volume. IVES at low frequencies (≤20 Hz) had a better modulatory effect than higher frequencies and the optimum duration of IVES was 5 min.

Conclusions

Evoked bladder contractions did not improve the IVES-induced modulation of the micturition reflex. These findings might help to improve the clinical application of the IVES procedure.

Keyword
bladder, electric stimulation, contraction, micturition reflex, rats
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13508 (URN)10.1046/j.1464-410x.1999.00947.x (DOI)
Available from: 1999-02-25 Created: 1999-02-25 Last updated: 2009-05-20
6. Prolonged enhancement of the micturition reflex in the cat by repetitive stimulation of bladder afferents
Open this publication in new window or tab >>Prolonged enhancement of the micturition reflex in the cat by repetitive stimulation of bladder afferents
1999 (English)In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 517, no 2, 599-605 p.Article in journal (Refereed) Published
Abstract [en]
  1. Prolonged modulation of the parasympathetic micturition reflex was studied in cats anaesthetized by -chloralose. Reflex discharges were recorded from a thin pelvic nerve filament to the bladder and evoked by stimulation of the remaining ipsilateral bladder pelvic nerves or urethral branches of the pudendal nerve.

     

  2. Stimulation of bladder or urethral afferents at A intensity evoked micturition reflexes with a latency of 90-120 ms. Such reflexes were much enhanced following repetitive conditioning stimulation of the same afferents at 20 Hz for 5 min.

     

  3. The reflex enhancement lasted more than 1 h after the conditioning stimulation. The effect was not prevented by a preceding complete transection of the sympathetic supply to the bladder. A prolonged suppression of the reflex was obtained after conditioning stimulation of afferents in the dorsal clitoris nerves.

     

  4. It is proposed that the prolonged modulations of the micturition reflex represent physiological adaptive processes, which preserve a flawless function of the bladder during life. The observations provide a theoretical explanation for the beneficial effect of electric nerve stimulation in patients with voiding disorders.
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13509 (URN)
Available from: 1999-02-25 Created: 1999-02-25 Last updated: 2017-12-13Bibliographically approved

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