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1 Division of Urology, The effect of capsaicin (10-80 mg/kg
sc) on reflex activity of the urinary bladder was examined in
anesthetized normal as well as anesthetized and awake chronic spinal
cord-injured (SCI) cats. In normal cats, capsaicin elicited a transient
increase in the frequency of isovolumetric bladder contractions and
reduced the volume threshold for inducing micturition, but did not
depress the amplitude of bladder contractions or the reflex firing on bladder nerves. In anesthetized SCI cats, capsaicin depressed reflex
bladder activity and firing on bladder nerves. In awake SCI cats,
capsaicin initially decreased the volume threshold for inducing
micturition; however, after a delay of 3-6 h the volume threshold
increased and intravesical voiding pressure decreased. This effect
persisted for 4-12 days. It is concluded that capsaicin-sensitive C fiber bladder afferents are not involved in initiating reflex micturition in normal cats, but play an essential role in
triggering automatic micturition in chronic SCI cats. The results
are consistent with the clinical data indicating that C
fiber bladder afferents contribute to bladder hyperactivity and
incontinence in patients with neurogenic bladder dysfunction.
urinary bladder; spinal cord injury; C fiber afferents; detrusor
hyprerreflexia
SPINAL CORD INJURY leads to a prominent reorganization
of the sacral parasympathetic reflex pathways underlying micturition in
the cat (7-12). In animals with an intact neuraxis, micturition is
mediated by a spinobulbospinal reflex pathway consisting of an afferent
and a preganglionic efferent limb in the pelvic nerve and central relay
centers in the sacral spinal cord and rostral pons (1, 7, 8, 12).
Afferent activity that triggers micturition in normal animals is
generated by tension receptors in the bladder wall and is carried to
the sacral spinal cord by myelinated axons (A The emergence of a C fiber afferent-evoked reflex in SCI cats is
dependent on peripheral and central changes in the reflex pathways (8,
9, 30). First, C fiber afferents are unresponsive to bladder distension
in normal cats (17) and therefore their peripheral receptor properties
must be altered so that they can respond to bladder distension in
chronic SCI animals. Second, the central synaptic connections of C
fiber afferents, which are weak in normal animals, must be strengthened
after spinal injury to account for the development of strong
micturition reflexes and the emergence of a hyperreflexic bladder in
SCI preparations (10, 11).
The present experiments were undertaken to evaluate further the role of
C fiber bladder afferents in micturition in normal and chronic SCI
cats. We attempted to chemically disrupt C fiber afferent functions by
administering capsaicin, a neurotoxin, which is believed to act
selectively on small diameter afferent neurons (23). The data indicate
that capsaicin-sensitive mechanisms are relatively unimportant for the
control of micturition in normal cats but play an essential role in
initiating micturition in chronic SCI cats. Preliminary accounts of the
results have appeared in an abstract (4).
Fifteen adult female and four male cats (2-3.5 kg) were used in
this study. All experiments on normal animals were conducted in
Urinary bladder activity was monitored by a catheter (PE-100 tubing)
inserted into the bladder through the urethra. The catheter was filled
with saline solution and connected to a strain gauge pressure
transducer to measure intravesical pressure. In some preparations, the
urethra or the urethral orifice was ligated to prevent bladder emptying
and thereby record isovolumetric bladder contractions. In other
experiments, the bladder was allowed to empty around the catheter.
Cystometrograms (CMGs; i.e., bladder pressure-volume curves) were
performed by infusing saline into the bladder through the catheter at a
moderate rate (1.23-2.47 ml/min) using an infusion pump. CMGs were
also performed on unanesthetized SCI animals, which were restrained in
a plastic cage during the experiment. The animals were briefly
(5-10 min) anesthetized with halothane to insert the urethral
catheter and then allowed to recover for 1 h before beginning
recordings. Before the experiment the animals were acclimated to the
cage during several trial sessions. In general the animals appeared
comfortable and remained quiescent during the recording sessions.
Spinal cord transections were performed using aseptic surgical
techniques under halothane anesthesia. The cord was exposed by a
laminectomy at the
T10-T12
segmental level, and then the cord and dura were cut leaving a wide gap
(3-4 mm) between the cut ends. Animals were treated
prophylactically with antibiotics (ampicillin 150 mg/kg im) for 1 wk,
and the bladder was expressed manually three to four times per day
until automatic micturition developed. Animals were studied 2-6 mo
after spinal transection. Experimental protocols were approved by The
University of Pittsburgh Animal Care and Use Committee.
Electrical recordings on vesical postganglionic nerves were performed
in chloralose-anesthetized cats as described previously (7, 12). In
brief, the bladder and its innervation were exposed by a midline
abdominal incision, and postganglionic nerves on the surface of the
bladder were prepared for monophasic, multiunit recording with bipolar
silver electrodes. The pelvic nerve was exposed and placed on bipolar
electrodes for stimulation of afferent and preganglionic efferent axons
with rectangular pulses (0.05-ms duration) of varying intensities
(0.5-50 V), frequencies (0.5-30 Hz), and patterns (single
shocks or trains, 30-100 Hz, 20- to 100-ms train duration).
Abdominal skin flaps were tied to a metal frame to form an abdominal
pool, and the area was covered with warm mineral oil. Cutaneous
afferent receptors in the perigenital area were stimulated by gently
stroking the skin with a cotton swab.
Neural activity was recorded with high-gain preamplifiers and displayed
on an oscilloscope or averaged on a digital computer and plotted on a
paper recorder. Bladder pressure, blood pressure, expired
CO2, and asynchronous neural
activity monitored with a window discriminator/ratemeter were displayed
on a rectilinear paper recorder.
Drugs
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
) (9, 19). In chronic
spinal cord-injured (SCI) cats micturition is mediated by a spinal
reflex pathway organized in the sacral cord and consisting of an
unmyelinated (C fiber) afferent limb (9, 11).
MATERIALS AND METHODS
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
-chloralose-anesthetized preparations (60 mg/kg iv) after induction
with halothane (2-3%). Chronic SCI cats were studied in both anesthetized (-chloralose) and unanesthetized preparations. In anesthetized preparations, a tracheal cannula was inserted to
facilitate respiration. Blood pressure was monitored via a catheter in
the common carotid artery. Fluids or drugs were administered by a
catheter in the femoral or cephalic vein. Some animals breathed spontaneously, whereas others were paralyzed with pancuronium bromide
(0.1-0.2 mg/kg iv) and artificially respired. Body temperature and
expired CO2 were maintained within
normal limits by external heating devices and by adjusting the rate and
depth of respiration, respectively.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Spinal Intact Cats
Effect of capsaicin on bladder activity. The acute and chronic effects (4-day pretreatment) of capsaicin (5-100 mg/kg sc) on CMGs and rhythmic isovolumetric bladder contractions were studied in 10 chloralose-anesthetized cats with intact spinal cords (Fig. 1). Untreated animals exhibited a wide range of bladder capacities (10-30 ml) and bladder contraction amplitudes (30-60 cmH2O). Similar responses were noted in animals (n = 3) pretreated 4 days before the experiment with a large dose of capsaicin (50-60 mg/kg sc).
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The acute administration of capsaicin during the experiment in doses
extending to the lethal level, mean 40 mg/kg (range 20-100 mg/kg
sc), did not depress the frequency, amplitude, or duration of rhythmic
bladder contractions recorded under isovolumetric conditions in the
distended bladder (15-50 ml) (Fig. 2).
The volume threshold for inducing the micturition reflex was also not
increased by acute capsaicin administration. Rather it was decreased
for a period of several hours (Fig.
1B). Similarly, during the initial period (20-40 min) after capsaicin injection, bladder activity recorded isovolumetrically was facilitated in some animals (Figs. 1 and
2). Baseline bladder pressure also increased (5-15
cmH2O). After the initial period
of stimulation, subsequent doses of capsaicin did not elicit an
increase in bladder activity.
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Effect of capsaicin on reflex activity in vesical
postganglionic nerves. Electrical recordings on vesical
postganglionic nerves revealed asynchronous firing in concert with
large-amplitude bladder contractions and synchronous discharges
occurring at short (15-25 ms) and long (90-140 ms) latencies
in response to electrical stimulation of the pelvic nerve (Fig.
3A). The
short-latency responses represent peripheral responses (PR), i.e.,
postganglionic firing elicited by stimulation of the preganglionic
pathways to the bladder, whereas the long-latency discharges reflect
central reflex responses (CR) elicited by stimulation of afferent axons
in the pelvic nerve. Both responses were blocked by ganglionic blocking
agents (hexamethonium, 1-5 mg/kg iv), indicating that they
represented firing in postganglionic nerves. Capsaicin (10-80
mg/kg sc) did not alter the early or late occurring discharges on
bladder postganglionic nerves (Fig. 3B).
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Chronic SCI Cats
CMGs in unanesthetized animals. Repeated CMGs were performed in three chronic SCI cats (2 males, 1 female) 2-6 mo after spinal cord transection and after the development of automatic micturition. Intravesical pressure was measured via a catheter inserted into the bladder through the urethral orifice. Several CMGs were performed during each recording session, and several recording sessions were conducted before the administration of capsaicin. The micturition volume thresholds varied considerably between the three animals (10-65 ml) but were reasonably consistent in the same animal. In two animals, low doses of capsaicin (5-10 mg/kg) initially stimulated bladder activity. This effect persisted for several hours after the injection of the drug. Injection of the capsaicin vehicle had no detectable effect. As shown in Fig. 4, the more delayed effect of capsaicin (10-50 mg/kg sc) was a significant increase in the volume threshold (mean, 77%; range 36.5-140%), a decrease in the amplitude of bladder contractions (mean, 49%, range 37.6-60%) (Fig. 5), and a marked decrease in volume of fluid voided. The minimum effective dose of capsaicin ranged from 10 to 30 mg/kg sc. The depressant effect of capsaicin was observed within 3-6 h after administration and persisted for 4-12 days. In one animal, bladder contraction amplitude recovered but the micturition volume threshold remained elevated for the duration of the study (1 mo). After capsaicin administration it was necessary to manually empty the bladders at regular intervals (6-8 h) because they were usually distended with urine. This indicates that capsaicin induces urinary retention. Before capsaicin treatment the bladders were less distended, presumably because they emptied by reflex voiding.
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Effect of capsaicin on bladder activity in
anesthetized animals. Isovolumetric bladder
contractions were recorded in four chronic SCI animals under chloralose
anesthesia (Figs. 6 and
7). The amplitudes of the bladder
contractions were less (50%) than those recorded in unanesthetized
animals just before anesthesia. Two of the animals had received
capsaicin treatment 30-45 days before the experiment. Rhythmic
bladder contractions in the four animals were markedly reduced in
amplitude by capsaicin (5-35 mg/kg sc) (Fig.
6D). A complete block of rhythmic
contractions occurred in doses between 10 and 50 mg/kg (Fig.
7C). Excitatory effects (Fig.
6B) with low doses (5-15 mg/kg)
of capsaicin were noted in two of four animals before the onset of the
depression. The amplitude and frequency of rhythmic, isovolumetric
contractions were reduced within 15-20 min after the injection of
capsaicin and remained depressed for the remainder of the experiment
(1-4 h). Injection of additional fluid into the bladder did not
reverse the depressant effect. However, tactile stimulation of the
perigenital region still excited the bladder (Fig.
8) when rhythmic bladder contractions were
abolished. The bladder contractions elicited by electrical stimulation
of preganglionic axons in the pelvic nerve were not depressed by
capsaicin (Fig. 8B).
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Effect of capsaicin on reflex activity in vesical
postganglionic nerves. Electrical stimulation of the
pelvic nerve in chronic SCI animals (n = 4) at intensities sufficient to activate A-fibers (0.75-4 V)
did not evoke central reflexes. However, stimulation at higher
intensities sufficient to activate C fiber afferents (5-30 V)
elicited long-latency (180-220 ms), prolonged discharges (CR;
100-150 ms), as well as short-latency, peripheral ganglionic responses (PR; Fig. 9,
A and
B). Capsaicin (5-25 mg/kg sc)
produced a rapid onset (15-25 min) depression of the late central
reflex (Fig. 9, B and
C) without altering the early
peripheral ganglionic response (Fig. 9,
C-E).
The depression remained for the duration of the experiment (2-3
h).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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The present experiments revealed that the effects of capsaicin on the urinary bladder of the cat are markedly influenced by spinal cord injury. In cats with an intact neuraxis, capsaicin administered systemically had primarily a facilitatory effect on reflex bladder activity, whereas in chronic SCI cats capsaicin had a prolonged depressant effect. These responses are consistent with the selective actions of capsaicin on small diameter afferents (23) and current concepts regarding the organization of micturition reflex pathways in normal and chronic SCI animals (7-10, 26).
The excitatory effects of capsaicin in the normal animal are most
reasonably attributed to stimulation of C fiber afferents in the
bladder (23). These afferents are of a high threshold type that do not
respond to bladder distension but do respond to noxious stimulation
such as chemical irritation (17). These afferents have been named
silent C fibers (17, 18, 23). Activation of nociceptive afferents by
the application of local irritants to the bladder facilitates the
micturition reflex and produces bladder hyperactivity (2, 5, 21, 24,
28, 32). This hyperactivity must occur at least in part by facilitation of the central reflex pathways. Because capsaicin is known to excite
and then desensitize C fiber afferents (23, 25), its facilitatory
effects on the bladder are likely to be elicited by a similar
mechanism. Activation of myelinated A-afferents that comprise the
afferent limb of the micturition reflex pathway in normal animals might
also contribute to the response, because some of these afferents can be
excited by capsaicin (23).
Large doses of capsaicin in normal animals produced a prolonged
facilitation of bladder activity and eventually desensitization of the
response to subsequent doses of capsaicin. However, bladder reflexes
were not blocked. This indicates that A-afferents in the cat, unlike
those in the rat (5, 23, 25), are resistant to the toxic effects of
capsaicin. In the rat, large doses of capsaicin blocked micturition for
12-18 h (5).
In chronic SCI cats that had developed automatic micturition, capsaicin depressed the micturition reflex. This was evident as an increase in the volume threshold for inducing micturition, a decrease in the amplitude of micturition contractions, as well as a depression of reflex activity on bladder postganglionic nerves and rhythmic bladder contractions in anesthetized animals. The depressant effects were preceded by a transient facilitation of bladder activity in 50% of the animals. The dose of capsaicin to elicit excitation was low (5-10 mg/kg sc) in both normal and chronic SCI animals, whereas the dose to suppress bladder activity in chronic SCI animals was higher (5-35 mg/kg sc). This is consistent with the findings that low concentrations of capsaicin excite and high concentrations desensitize or block C fiber afferent nerves.
It is clear that the effects of capsaicin in chronic SCI cats were affected by chloralose anesthesia. In anesthetized animals capsaicin could completely block the micturition reflex, whereas in unanesthetized cats capsaicin reduced the micturition reflex and increased the bladder volume threshold for inducing micturition but never completely blocked reflex activity. This difference is most reasonably attributable to a synergistic interaction between the anesthetic and capsaicin. Anesthetics are known to suppress the micturition reflex and to have a greater effect in chronic SCI animals than in animals with intact neuraxes (6, 31). Furthermore, in the present study, when bladder activity was recorded in the same cat before and after the administration of chloralose, it was noted that the anesthetic reduced the amplitude of reflex bladder contractions. Thus autonomic synapses in the spinal cord already partially depressed by anesthesia may be more susceptible to a reduction of afferent input induced by capsaicin.
The present experiments indicate that capsaicin administered systemically may act at multiple sites to reduce bladder activity. On the basis of the extensive literature (23, 24) regarding the selective neural actions of capsaicin, it seems reasonable to assume that the toxin depresses C fiber afferent input to the spinal cord from tension receptors in the bladder wall. It is clear that capsaicin does not affect the efferent pathway to the bladder, because it did not alter 1) the postganglionic nerve action potentials or the bladder contractions evoked by preganglionic nerve stimulation, 2) the reflex bladder contractions and postganglionic nerve firing elicited by tactile stimulation of myelinated somatic afferent nerves in the perineum, or 3) bladder reflexes in normal cats. Because the same parasympathetic efferent pathway mediates the micturition reflex in normal cats as well as the C fiber bladder reflex in chronic SCI cats, a selective effect of capsaicin on the latter must be due to an action on the afferent limb of the pathway. However, on the basis of data from experiments in which the afferent axons in the pelvic nerve were electrically stimulated, it seems reasonable to propose that the depression of the evoked reflexes by capsaicin must have been due to the action of the toxin on the afferent axons in the peripheral nerves and dorsal roots or on the central afferent terminals in the spinal cord. An alternate explanation is that the electrically evoked reflexes depend on facilitation produced by tonic afferent activity arising in the bladder. Depression of this putative tonic activity by capsaicin would then indirectly reduce the evoked reflexes. This mechanism seems less likely because the C fiber-evoked bladder reflex in chronic SCI cats (11) can be elicited when the bladder is empty, and therefore the activation of this reflex pathway does not appear to depend on facilitation by tonic bladder afferent input.
Capsaicin might have multiple effects on C fiber bladder afferents, including 1) initial stimulation followed by acute desensitization of the afferent terminals and block of afferent firing, 2) depletion of neuropeptide transmitters in the afferents, and 3) degeneration of the afferent terminals in the bladder wall or in the spinal cord (23, 24). The effect of capsaicin to produce an initial stimulation of the bladder consisting of a decrease in the micturition volume threshold during CMGs and an increase in the frequency and amplitude of rhythmic bladder contractions under isovolumetric conditions supports the view that capsaicin stimulates C fiber afferents and that these afferents can facilitate voiding function in the cat. The more prolonged depressant effects of capsaicin on micturition are likely to be due either to loss of transmitter stores and/or afferent terminal degeneration. Neuropeptides such as substance P, vasoactive intestinal polypeptide (VIP), and pituitary adenylate cyclase activating peptide have been identified in bladder afferents and/or implicated in bladder reflex mechanisms (9, 10). VIPergic afferents have attracted considerable attention in regard to bladder reflexes in paraplegic cats, because VIP-containing afferents form a very prominent projection to the sacral parasympathetic nucleus (20) and VIP is localized specifically to C fiber afferents at the sacral level of the spinal cord of cats (27). In addition, in SCI cats the intrathecal injection of VIP elicits a strong excitatory effect on bladder reflexes that is not seen in normal cats (10). Thus it has been proposed (8, 10) that plasticity in VIPergic, C fiber bladder afferent pathways may underlie the emergence of the C fiber micturition reflex in chronic SCI cats.
In normal cats it appears that the C fiber-evoked bladder reflex is
relatively unimportant in the control of micturition because capsaicin
treatment did not suppress bladder activity. This is consistent with
the observation that C fiber bladder afferents in the cat are silent
and do not respond to bladder distension (17). However, in the rat a
subpopulation of C fiber bladder afferents does respond to mechanical
stimuli (28, 29). Thus capsaicin does alter voiding function in rats
with an intact neuraxis even though micturition is triggered primarily
by A bladder afferents (5, 23-26). After spinal cord injury in
the rat, A bladder afferents continue to play a major role in
the initiation of micturition (26). Therefore capsaicin treatment
in paraplegic rats does not block voiding as noted in the cat but does
reduce bladder hyperreflexia and bladder sphincter dyssynergia (3, 6).
Clinical studies in which capsaicin was tested on patients with neurogenic bladder hyperactivity have demonstrated a number of similarities between cats and humans. For example, in patients with multiple sclerosis (14, 15) or traumatic injuries of the spinal cord exhibiting detrusor hyperreflexia and urge incontinence (13), intravesical administration of a concentrated (1-2 mM) capsaicin solution increased bladder capacity and reduced urinary frequency, urgency, and incontinence. The effect of capsaicin was prolonged, persisting many weeks to months, indicating that it is likely due to degeneration of afferent fibers in the bladder wall. This observation led to the proposal that neurogenic bladder hyperactivity in humans is also triggered by C fiber afferents (8, 9, 13-15).
Damage to central neural pathways also unmasks other types of reflexes mediated by C fiber bladder afferents. The introduction of cold water into the bladder of patients with spinal cord injury or multiple sclerosis induces reflex voiding (16). Cold stimulation has no effect in neurologically normal patients but does trigger voiding in neonates. This suggests that the cold-evoked reflex is a primitive spinal reflex pathway that is expressed in the immature spinal cord, disappears during postnatal development, and then reappears after damage to the spinal cord (16). Electrophysiological studies in cats have revealed that cold temperatures activate C fiber afferents in the bladder (22). Because intravesical capsaicin treatment suppresses cold-induced bladder reflexes in patients with neurogenic bladder dysfunction it seems reasonable to believe that these reflexes in humans as in cats are triggered by C fiber afferents.
In summary, the present experiments have revealed that systemic or
intravesical administration of capsaicin can suppress bladder hyperactivity and C fiber afferent-evoked parasympathetic reflexes to
the urinary bladder of the chronic SCI cat. Capsaicin did not block
A-afferent-evoked supraspinal reflexes in cats with an intact
neuraxis. It is concluded that in the cat as well as humans (13-15) that spinal cord injury causes a marked reorganization of
the reflex pathways controlling the urinary bladder, leading to the
emergence of primitive spinal reflex mechanisms that are triggered by
an unusual type of "silent" C fiber afferent. Thus automatic
micturition in paraplegic cats is likely to be a useful model system
for testing new therapies for the treatment of neurogenic disorders of
the lower urinary tract.
Perspectives
Considerable attention has been focused on capsaicin-sensitive C fiber afferents because they are important targets in the treatment of pain (24). However, these afferents can also trigger autonomic reflexes and induced visceral dysfunction. The ability of bladder nociceptive afferents to induce hyperactive voiding is not surprising, when one considers that the most effective response of the bladder to infection or to irritant substances in the urine would be increased voiding frequency. Thus C fiber-evoked bladder reflexes are most reasonably viewed as primitive defense mechanisms to trigger bladder emptying. Why neurological diseases, such as multiple sclerosis, or spinal cord injury cause the emergence of spinal C fiber-mediated voiding reflexes is not known. However, this may occur in response to elimination of bulbospinal pathways followed by reorganization of synaptic connections in the cord. It is also known that ion channel expression in bladder afferent neurons is changed after spinal cord injury (30). This increases neuronal excitability and might allow nociceptive afferents to respond to nonnoxious bladder distension. It has been speculated that this afferent plasticity occurs indirectly as a result of uncoordinated bladder-sphincter activity, which increases urethral outlet resistance, followed by bladder hypertrophy and increased levels of neurotrophic factors in the bladder. The latter in turn can induce changes in neuronal properties. Regardless of the mechanism underlying the emergence of C fiber-evoked bladder hyperactivity, it is clear from clinical studies (14-16) that C fiber afferents are important targets for drug therapy of detrusor hyperreflexia and that intravesically administered capsaicin can be used to treat this disorder.| |
ACKNOWLEDGEMENTS |
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This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-49430 and Taiwan Grant NSC-87-2314-B-075A-011 and NSC-88-2314-B-075A-011.
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: C.-L. Cheng, Division of Urology, Dept. of Surgery, Taichung Veterans General Hospital, Taichung 407, Taiwan (E-mail: clcheng{at}vghtc.vghtc.gov.tw).
Received 8 February 1998; accepted in final form 25 May 1999.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Barrington, F. J. F.
The component reflexes of micturition in the cat. Parts I and II.
Brain
54:
177-188,
1931
2.
Birder, L. A.,
and
W. C. de Groat.
Increased c-fos expression in spinal neurons after chemical irritation of the lower urinary tract of the rat.
J. Neurosci.
12:
4878-4889,
1992[Abstract].
3.
Cheng, C.-L.,
and
W. C. de Groat.
The effects of capsaicin on micturition and associated reflexes in the rat.
Soc. Neurosci. Abstr.
13:
270,
1987.
4.
Cheng, C.-L.,
and
W. C. de Groat.
Changes in the afferent pathway for the micturition reflex after spinal cord injury in the cat (Abstract).
J. Urol.
157:
80,
1997.
5.
Cheng, C.-L.,
C.-P. Ma,
and
W. C. de Groat.
Effects of capsaicin on micturition and associated reflexes in the rat.
Am. J. Physiol.
265 (Regulatory Integrative Comp. Physiol. 34):
R132-R138,
1993
6.
Cheng, C.-L.,
C.-P. Ma,
and
W. C. de Groat.
Effect of capsaicin on micturition and associated reflexes in chronic spinal rats.
Brain Res.
678:
40-48,
1995[Medline].
7.
De Groat, W. C.
Nervous control of the urinary bladder of the cat.
Brain Res.
87:
201-211,
1975[Medline].
8.
De Groat, W. C.
Mechanisms underlying the recovery of lower urinary tract function following spinal cord injury.
Paraplegia
33:
493-505,
1995[Medline].
9.
De Groat, W. C.,
A. M. Booth,
and
N. Yoshimura.
Neurophysiology of micturition and its modification in animal models of human disease.
In: The Autonomic Nervous System, Nervous Control of the Urogenital System, edited by C. A. Maggi. London: Harwood Academic, 1993, vol. 3, p. 227-290.
10.
De Groat, W. C.,
M. Kawatani,
T. Hisamitsu,
C.-L. Cheng,
C.-P. Ma,
K. Thor,
W. Steers,
and
J. R. Roppolo.
Mechanisms underlying the recovery of urinary bladder function following spinal cord injury.
J. Auton. Nerv. Syst.
30:
S71-S77,
1990.
11.
De Groat, W. C.,
I. Nadelhaft,
R. J. Milne,
A. M. Booth,
C. Morgan,
and
K. Thor.
Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine.
J. Auton. Nerv. Syst.
3:
135-160,
1981[Medline].
12.
De Groat, W. C.,
and
R. W. Ryall.
Reflexes to sacral parasympathetic neurones concerned with micturition in the cat.
J. Physiol. (Lond.)
200:
87-108,
1969
13.
De Seze, M.,
L. Wiart,
P.-A. Joseph,
J.-P. Dosque,
J.-M. Mazaux,
and
M. Barat.
Capsaicin and neurogenic detrusor hyperreflexia: a double-blind placebo-controlled study in 20 patients with spinal cord lesions.
Neurourol. Urodyn.
17:
513-523,
1998[Medline].
14.
Fowler, C. J.,
R. O. Beck,
S. Gerard,
C. D. Betts,
and
C. G. Fowler.
Intravesical capsaicin for treatment of detrusor hyperreflexia.
J. Neurol. Neurosurg. Psychiatry
57:
169-173,
1994
15.
Fowler, C. J.,
D. Jewkes,
W. I. McDonald,
B. Lynn,
and
W. C. de Groat.
Intravesical capsaicin for neurogenic bladder dysfunction.
Lancet
339:
1239,
1992[Medline].
16.
Geirsson, G.,
M. Fall,
and
S. Lindström.
The ice water test: a valuable and simple supplement to routine cystometric investigation.
Br. J. Urol.
71:
681-685,
1993[Medline].
17.
Habler, H. J.,
W. Janig,
and
M. Koltzenburg.
Activation of unmyelinated afferent fibres by mechanical stimuli and inflammation of the urinary bladder in the cat.
J. Physiol. (Lond.)
425:
545-562,
1990
18.
Jänig, W.,
and
M. Koltzenburg.
Pain arising from the urogenital tract.
In: The Autonomic Nervous System, Nervous Control of the Urogenital System, edited by C. A. Maggi. London: Harwood Academic, 1993, vol. 3, p. 525-578.
19.
Jänig, W.,
and
J. F. B. Morrison.
Functional properties of spinal visceral afferents supplying abdominal and pelvic organs, with special emphasis on visceral nociception.
Prog. Brain Res.
67:
87-114,
1986[Medline].
20.
Kawatani, M.,
S. L. Erdman,
and
W. C. de Groat.
Vasoactive intestinal polypeptide and substance P in primary afferent pathways to the sacral spinal cord of the cat.
J. Comp. Neurol.
241:
327-347,
1985[Medline].
21.
Koltzenburg, M.,
and
S. B. McMahon.
Plasma extravasation in the rat urinary bladder following mechanical, electrical and chemical stimuli: evidence for a new population of chemosensitive primary sensory afferents.
Neurosci. Lett.
72:
352-356,
1986[Medline].
22.
Lindström, S.,
and
L. Mazieres.
Effect of menthol on the bladder cooling reflex in the cat.
Acta Physiol. Scand.
141:
1-10,
1991[Medline].
23.
Maggi, C. A.
The dual, sensory and efferent function of the capsaicin-sensitive primary sensory nerves in the bladder and urethra.
In: The Autonomic Nervous System, Nervous Control of the Urogenital System, edited by C. A. Maggi. London: Harwood Academic, 1993, vol. 3, p. 383-422.
24.
Maggi, C. A.,
and
A. Meli.
The sensory-efferent function of capsaicin-sensitive sensory neurons.
Gen. Pharmacol.
19:
1-43,
1988[Medline].
25.
Maggi, C. A.,
P. Santicioli,
S. Giuliani,
M. Furio,
and
A. Meli.
The capsaicin-sensitive innervation of the rat urinary bladder: further studies on mechanisms regulating micturition threshold.
J. Urol.
136:
696-700,
1986[Medline].
26.
Mallory, B.,
W. D. Steers,
and
W. C. de Groat.
Electrophysiological study of micturition reflexes in rats.
Am. J. Physiol.
257 (Regulatory Integrative Comp. Physiol. 26):
R410-R421,
1989
27.
Morgan, C.,
and
P. Ohara.
Electron microscopic identification of vasoactive intestinal polypeptide (VIP) in visceral primary afferent axons in the sacral spinal cord of cat (Abstract).
Anat. Rec.
208:
121,
1984.
28.
Morrison, J. F. B., S. Namasivayam, and I. Eardley.
ATP may be a natural modulator of the sensitivity of bladder
mechanoreceptors during slow distensions.
Abstr. 1st
Int. WHO Consultation on Incontinence: 84, 1998.
29.
Sengupta, J. N.,
and
G. F. Gebhart.
Mechanosensitive properties of pelvic nerve afferent fibers innervating the bladder of the rat.
J. Neurophysiol.
72:
2420-2430,
1996
30.
Yoshimura, N.,
and
W. C. de Groat.
Plasticity of Na+ channels in afferent neurones innervating rat urinary bladder following spinal cord injury.
J. Physiol. (Lond.)
503:
269-276,
1997
31.
Yoshiyama, M.,
J. R. Roppolo,
and
W. C. de Groat.
Alterations by urethane of glutamatergic control of micturition.
Eur. J. Pharmacol.
264:
417-425,
1994[Medline].
32.
Yu, Y.,
and
W. C. de Groat.
Effects of ZD6169, a K-ATP channel opener, on bladder hyperactivity and spinal c-fos expression evoked by bladder irritation in rats.
Brain Res.
807:
11-18,
1998[Medline].
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