TOPICAL EFFECTS OF INTRAVESICAL CAPSAICIN ON RAT BLADDER

Investigative Urology
Brazilian Journal of Urology
Vol. 28 (2): 154-158, March - April, 2002
Official Journal of the Brazilian Society of Urology
TOPICAL EFFECTS OF INTRAVESICAL CAPSAICIN ON RAT BLADDER
AYHAN VERIT, OKTAY ARSLAN, ILYAS OZARDALI, ERCAN YENI, DOGAN UNAL
Departments of Urology, Pharmacology and Pathology, Harran University Medical School, Sanliurfa, Turkey
ABSTRACT
Background: To determine the topical effect of intravesical capsaicin on bladder mucosa in graded
doses.
Methods: Intravesical reagent was instilled in four groups of age and weight matched female rats: 2, 4
and 40 mM capsaicin and saline. Intravesical capsaicin was dissolved in 30% ethanol (EtOH) and saline. The
animals (n = 4 each group) were sacrificed at the 13th day after a total of 5 instillations at days 0, 2, 5, 7 and 10.
Whole bladders were harvested, fixed in 10% buffered formalin, and paraffin embedded. Tissue blocks were
blind coded and sectioned (5-mm thickness) for histopathological analysis. All sections were stained with
hematoxylin and eosin and examined under light microscopy. Fishers’ exact test was used for statistical ana-
lyze.
Results: The rats in intravesical capsaicin groups (2, 4, and 40 mM) exhibited similar bladder mucosal
histology. Instillation of saline demonstrated no effect on bladder histology, whereas instillation of intravesical
capsaicin induced acute thinning effect of the epithelium, submucosal edema, vascular ectasia and congestion
and also eosinophil infiltration, that was statistically insignificant, in some parts of the stroma of only one
bladder (25%) in the 40 mM group.
Conclusions: All bladders in intravesical capsaicin groups demonstrated a histologically similar mucosa,
except for the eosinophil infiltration in some parts of the stroma of a bladder in 40 mM group and which was
statistically insignificant. Thus, we conclude that, in the resistant cases treated with intravesical capsaicin,
concentrations may be risen up above the widely used doses, if an adequate anesthesia is maintained.
Key words: bladder; urinary bladder; rat; cystitis; capsaicin
Braz J Urol, 28: 154-158, 2002
INTRODUCTION
lower urinary tract and severe bladder pain (2). In
animal models, capsaicin has a neurotoxic effect on
Red hot chili was introduced in human diet
unmyelinated C fibers by binding vanilloid receptors
in Mexico 7000 years ago. Capsaicin is a pungent
located in the bladder mucosa (3). Through the study
substance which is a derivative of homovanillic acid
of the spinal of cats, it has observed that capsaicin
and is chemically represented by 8-methyl-N-
blocks the micturation reflex initiated by the C fibers,
vannilyl-6-nonenamide found in red hot chili peppers
which are also responsible for the transmission of pain
(1). A solution of pure capsaicin powder can be made
to the spinal cord reducing hyperreflexia (4). A 1 - 2
by dissolving it in alcohol and saline. For about the
mmol/l (0.3 - 0.6 g/l) capsaicin solution is widely
last decade, intravesical capsaicin has been taken into
accepted for intravesical treatment of detrusor
account in urology clinics as a treatment option in
hyperreflexia and it should be considered that the
detrusor hyperreflexia, hypersensitive disorders of the
concentrations used for hypersensitive bladder are
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TOPICAL EFFECTS OF INTRAVESICAL CAPSAICIN
about 100 times lower than those used for
Statistical analysis was performed with Fisher exact
hyperreflexia (5). Recently, it has been reported that
test.
capsaicin is no better than placebo for relieving
bladder pain, and it was suggested that higher
RESULTS
concentrations of capsaicin for painful bladder might
be more effective, if adequate anesthesia is maintained
During the study all animals survived. No
during the procedure (6). Pain, during and sometimes
systemic signs of toxicity, loss of weight and fur was
after the instillations, is still a common problem in
observed. Urinalysis was performed in all animals
the intravesical use of this drug. Topical capsaicin in
post-intravesical instillation and no animals developed
a concentration range of 0.01 to 30.0 mM has been
a urinary tract infection. Instillation of capsaicin in
used to treat many painful conditions, including
either doses had the same effect on the bladder
postherpethic neuralgia and painful diabetic
mucosa, similar to chemical cystitis, such as acute
neuropathy (7,8). In this study, we studied the topical
mucosal injury, submucosal edema, vascular ectasia,
effects of intravesical capsaicin in graded doses on
vascular congestion and thinning of the epithelium,
rat bladder mucosa.
but not mucosal ulceration (Parts A, B and C of
Figure-1). Eosinophil infiltration was noticed in some
MATERIALS AND METHODS
parts of the stroma in one bladder (25%) in the very
high dose group (Figure-2). This was statistically
Animal model: Intravesical reagents were
insignificant (p = 1). The bladders in control group
instilled in four groups (four animals in each group)
did not show any pathology (Part D of Figure-1).
of Wistar female rats. Intravesical agents were studied
as: 1)- control (intravesical saline only); 2)- normal
DISCUSSION
dose, 2 mmol/l (0.6 g/l) of capsaicin; 3)- high dose, 4
mmol/l (1.2 g/l) of capsaicin; 4)- very high dose, 40
It is well known that capsaicin has been a
mmol/l (12 g/l) of capsaicin. Rats were matched for
constituent of human diet for thousands of years
age and weight (230-260 grams). Ketamin HCL
without any long-term side effects (9). In painful
anesthesia was used during intravesical instillation
conditions such as postherpethic neuralgia and painful
and bladder harvesting.
diabetic neuropathy, topical capsaicin has been used
Intravesical instillation: Ruling out urinary
in a range of concentrations between 0.01 to 30.0 mM.
tract infection through urinalysis was performed. So-
(7,8). Neither systemic absorption of capsaicin after
lutions of capsaicin were prepared in 30% ethanol
single or repeated administration nor evidence of
(EtOH). The bladder was catheterized through the ure-
permanent damage to nerves or tissues in the treated
thra and emptied. The intravesical instillation con-
area was observed (10). Burning sensation at the site
sisted of 1 ml solution of each reagent into the blad-
of application is the most reported complaint (11).
der via urethral catheterization. Some leakage was
Most patients with intractable detrusor hyperreflexia
observed. The bladder was emptied 30 minutes after
would be treated with indwelling catheters and those
the reagent instillation. Each group contained 4 ani-
disabled would be submitted to operative procedures
mals, which were all sacrificed at the 13th day after a
to achieve continence. Therefore, intravesical
total of 5 instillations at the days 0, 2, 5, 7 and 10.
capsaicin as an effective therapy for detrusor
Whole bladders were harvested, fixed in 10% buff-
hyperreflexia became popular in urological practice.
ered formalin and embedded in paraffin.
In animal experiments, it was shown that
Histopathological analysis: Tissue blocks
response to intravesical capsaicin depends on the
were blind coded and sectioned in 5-µm-thick cuts
concentrations (12). Tolerable intravenous capsaicin
for histological staining with hematoxylin and eosin
for adults is about 0.3 mg in the literature (13). So it
(HE). Samples were examined under light microscopy
is widely accepted, but not consistent, that the
at magnifications of X100 and X200.
maximum intravesical concentrations of capsaicin is
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TOPICAL EFFECTS OF INTRAVESICAL CAPSAICIN
A
B
C
D
Figure 1 - A)- to C)- Bladder histology of rats in intravesical capsaicin groups, submitted to graded doses of 2, 4 and 40 mM,
respectively. The alterations include acute mucosal injury, thinning of the epithelium, submucosal edema, vascular ectasia, and conges-
tion; D)- Control group after instillation of saline demonstrated no effect on the bladder mucosa. (HE, A and D, X100; C and D, X200).
2 mmol/l because of the systemic absorptions of the
of capsaicin (15). Although the instillation of lidocain
agent by the bladder wall (5). In our study, even though
2% before capsaicin made the procedure easier, it did
we reach to the intravesical dose of 40 mmol/l, we
did not observe any systemic complication. Local side
effects of capsaicin as suprapubic or urethral pain,
burning sensation, gross hematuria, urgency appears
during and for several days after the instillation, and
resolve within either 1 - 3 days in nonneurologic
patients or 15 days in neurologic ones (2).
Tachyphylaxis to the burning lasted mostly not more
than 72 hours, but may go on to a time of 4 weeks (11).
While general anesthesia seems to be not
helpful because the agents used would not relax the
detrusor in spinal cord injury patients (14) and epidural
anesthesia needs specialist assistance, use of local
anesthesia appears to be the best option because of its
Figure 2 - Eosinophil infiltration in the stroma of one bladder of
better general tolerance without affecting the efficacy
the very high dose capsaicin instillation group. (HE, X200).
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TOPICAL EFFECTS OF INTRAVESICAL CAPSAICIN
not provide adequate local anesthesia in all patients.
der with capsaicin: Is it safe? Eur Urol, 33: 28-
Electromotive drug administration (EMDA) of lidocain
31, 1998.
in local anesthesia was offered for these patients as
2. De Seze M, Wiart L, Ferriere JM, De Seze MP,
simple office technique, that does not require
Joseph PA, Barat M: Intravesical instillation of
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in a case control epidemiological study, where
Mele A: The role of capsaicin-sensitive innerva-
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C, Ma CP, Thor K: Mechanisms underlying the
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Received: January 14, 2002
Accepted: March 1, 2002
Correspondence address:
Dr. Ayhan Verit
Harran Univ. Tip Fak. Hastanesi
Tr-63100 Sanliurfa, Turkey
Fax: + + (90) (414) 316-8831
E-mail: averit@ixir.com.tr
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