Neuromodulation techniques in the treatment of the

overactive bladder

J. CROEN and J.L.H.R. BOSCH

Department af Uralagy, Erasmus MedicalCenter Rotterdam, RotterdClln, The Netherlcmds

Introduction

Symptoms of an overactive bladder often remain a

therapeutic problem despite optimal use of conservative

treatment methods induding drug therapy, behavioural

therapy, pelvic fioor exercises and biofeedback. In the lapt

decade, sacral nerve neuromodulation has been con-

firmed as a valuable addition to the therapeutic arsenal.

The success of sacral neuromodulation has renewed

interest in other neuromodulation techniques. The

current techniques of neuromodulation for treating the

overactive bladder are:

. anogenital electrical stimulation;

. transcutaneous electrical nerve stimulation (TENS);

. sacral nerve neuromodulation;

. percutaneous posterior tibia! nerve stimulation (Stoller

afIerent nerve stimulation, SANS);

. magnetic stimulation.

Mechanism of action

It is unknown how neuromodulation works; indeed, it is

even unknown whether neuromodulation only works at

the spinal levei or whether supraspinal pathways are

involved [1]. The most important spinal inhibitory

mechanisms of the micturition refiex are [2]:

. The guarding refiex: increased activity of the striated

urethral sphincter in response to bladder filling,

refiexively inducing detrusor relaxation;

. Edvardsen's refiex: increased activity of the sympa-

thetic nervous system in response to bladder filling;

. Anal dilatation (afIerent pathway: anorectal branches

ofthe pelvic nerve; prevents voiding during defecation);

. Gentle. mechanical stimulation of the genital

region (afIerent pathway: dorsal 'ditora! or penile

branches of the pudendal nerve; prevents voiding

during intercourse);

Accepted for publication 1 March 2001

. Physical activity; alferent pathway: musde afIerents

from the ümbs (but not from the pelvic fioor!; prevents

voiding during fighting or fleeing);

Most oE the afIerent fibres involved in the above

inhibitory mechanisms reach the spinal cord via the

dorsal roots of the sacral nerves. Edvardsen's refiex can

also be activated by stimulation of afferent anorecta!

branches ofthe pelvic nerve and afferent dorsal clitoral or

penile branches of the pudenda! nerve, at least in cats. Its

role in humans is probably limited [3].

At least two potential mechanisms are possible: (i)

activation of elferent fibres to the striated urethra!

sphincter refiexively cause detrusor relaxation; and (ü)

activation of afferent fibres causes inhibition at a spinal or

a supraspinal leveI. Based on experiments in dogs and

observations in humans, Tanagho and Schmidt [4], who

introduced sacral neuromodulation into the field of

urology, adhered to the first theory. However, measure-

ments of the urethral pressure profile and af urethral

resistance during voiding do not indicate that the striated

sphincter is activated with the stimulation parameters

currently used [5]. Interesting studies supporting the

second theory are those in which the dorsal clitoral or

dorsal penile nerve, purely afferent branches of the

pudendal nerve, were electrically stimulated. This

induced a ~tr~ng inhibition of the mi~turition reflex

and detrusor hyper-refiexia in healthy volunteers and

patients with a hyper-refiexive bladder [6-8]. Fowler et a!.

[9] measured the latency of the anal sphincter contrac-

tion during a peripheral nerve evaluation (PNE) test in

women who were candidates for sacral neuromodula-

tion, and conduded that this response was mediated by a

polysynaptic reflex rather than the result of efferent

stimulation. Experimental work in spinalized rats showed

that neuromodulation reduced the degree of hyper-

reflexia as well as the expression of c-Jas after bladder

instillation with acetic acid [lQi(C-fos protein is

expressed in the spinal cord after frri1ation of the lower

urinary tract; this expression is mainly mediated by

afIerent C fibres). This resuIt shows that inhibition of

afferent C fibre activity may be one of the underIying