BASIC SCIENCE

INTRACAVERNOUS PRESSURE RESPONSES TO PHYSICAL

AND ELECTRICAL STIMULATION OF THE CAVERNOUS
NERVE IN RATS
JAMIL REHMAN, GEORGE CHRIST, ARNOLD MELMAN, AND JONATHAN FLEISCHMANN

ABSTRACT
Objectives. To better define the techniques of nerve-sparing prostate dissection that would result in
preservation of erectile function, we characterize the effects of physical pressure on the prostate and
cavernous nerve, electrical stimulation of the cavernous nerve, and pharmacologic manipulations on intra-
cavernous pressure (ICP) in normal and diabetic rats.
Methods. Fischer-34 rats, both normal and diabetic, underwent dissections that isolated the cavernous
bodies and cavernous nerves. Cavernous body pressures were characterized during surgical manipulation,
during electrical stimulation of the cavernous nerves, and following papaverine hydrochloride injection.
Results. In normal rats, baseline cavernous pressures ranged from 5 to 15 cm H2O (mean 12.29). In diabetic
rats, the baseline pressure was significantly lower (3 to 7.5 cm H2O). Lateral nerve displacement caused ICP
to rise to approximately 35 cm H2O in normal rats, but only to 20 cm H2O in diabetic rats. Electrostimulation
resulted in cavernous pressure increases of 10-fold from baseline in normal rats and sevenfold from baseline
in diabetic rats. ICPs were not disturbed appreciably with nerve-sparing dissection techniques. Neurotomy
resulted in declines in baseline cavernous pressures in all rats. Electrostimulation of the distal end of a
severed nerve resulted in pressure rises to 50% of those observed in rats with intact cavernous nerves.
Intracavernous papaverine injection before or after nerve stimulation masked subsequent (expected) pres-
sure changes.
Conclusions. A change in cavernous pressure is a sensitive indicator of cavernous nerve manipulation. Both
cavernous pressure measurements and electrostimulation of cavernous nerves may aid surgeons during
radical prostatectomy. UROLOGY 51: 640–644, 1998. © 1998, Elsevier Science Inc. All rights reserved.

W alsh and coworkers1,2 popularized the ana-

tomic approach to radical prostatectomy, a
technique designed to spare the cavernous nerves
pressure (ICP) measurements under various surgi-
cal and experimental conditions in rats.

and preserve erectile function. Impotence, how- MATERIAL AND METHODS

ever, continues to be a postoperative consequence
for many patients who undergo this operation,
even if the nerves were thought to have been
spared. Although vascular injury during prostatec-
tomy contributes to impotence in some patients,
unrecognized nerve injury is the probable cause for
impotence in the majority of patients. To better
define the limits of cavernous nerve manipula-
tions, we explored the utility of intracavernous
From the Department of Urology, Albert Einstein College of Med-
icine/Montefiore Medical Center, Bronx, New York
Reprint requests: Jonathan Fleischmann, M.D., Albert Einstein
College of Medicine, Department of Urology, Weiller Hospital of
AECOM, 1825 Eastchester Road, Room 2S 62, Bronx, NY 10461
Submitted: July 14, 1997, accepted (with revisions): October
14, 1997
ANIMALS
Two-month-old male Fischer-34 rats (Taconic Farms, Ger-
mantown, NY) were fed Purina rodent chow ad libitum and
housed individually with a 7 AM to 7 PM light cycle. The ani-
mals were divided into three groups: group 1 consisted of
control rats (n 5 10); group 2 consisted of diabetic rats (n 5
5); and group 3 consisted of rats who received physical and
neurostimulation after intracavernous injection of papaverine
hydrochloride (Eli Lilly) (n 5 10). (A total of 10 diabetic rats
were included at the outset of this study; 4 died within 3
months of induction of diabetes and 1 died during surgical
dissection; therefore, the results of 5 diabetic rats are available
for this study.)
INDUCTION OF DIABETES
Diabetes mellitus was induced for 3 months in 5 animals by
one intraperitoneal injection of streptozotocin (STZ; 35 mg/
kg, Sigma Chemicals) dissolved in citrate buffer (0.1 M citric

© 1998, ELSEVIER SCIENCE INC. 0090-4295/98/$19.00

640 ALL RIGHTS RESERVED PII S0090-4295(97)00693-6
FIGURE 1. The in vivo rat model used in this study. The rat is anesthetized and lying supine. The arterial line in the
left carotid artery is connected to a MacLab data acquisition board via a transducer and transducer amplifier, for
continuous monitoring of blood pressure. A right external jugular venous line is used for intravenous fluid transfusion
or blood sampling. The prostate has been exposed and the cavernous nerves are seen on the posterolateral surface
of the prostate arising from the pelvic ganglion, which is formed by the joining of the hypogastric and pelvic nerves.
The two corpora cavernosum have been exposed. A line is inserted into the right corpus cavernosum for continuous
monitoring of intracorporal pressure via the MacLab instrumentation and the second line is inserted in the left
corpora cavernosum for intracavernous drug injection. Finally, the nerve stimulator probe is placed around the
cavernous nerve for current stimulation.

acid 60 mL, 0.2 M Na2HPO4, 40 mL). Rats became hypergly-
cemic within 24 hours. The extent of diabetes was monitored
weekly by urine glucose analysis using a Labstix indicator
(Amesdiastix, Miles, Elkhartin), and also confirmed at death
by glucose analysis of blood obtained from cardiac puncture
(Chemstrip, Boehringer Mannheim, Germany).
SURGICAL TECHNIQUE FOR IN VIVO PRESSURE
MONITORING
Anesthesia and surgical preparation were performed 12
weeks after the induction of experimental diabetes (the time
when documented autonomic neuropathy as well as sensory
neuropathy3 is known to be present in diabetic rats). Anesthe-
sia was induced in both age-matched controls and diabetic
animals by intraperitoneal injection (35 mg/kg) of sodium
pentobarbital (Anpro Pharmaceuticals). Anesthesia was main-
tained during the course of the experimental protocol (2 to 3
hours) by subsequent injection of pentobarbital (5 to 10 mg/
kg) every 45 to 60 minutes, as required for maintenance of
anesthesia.
PLACEMENT OF PRESSURE MONITORING CANNULAE
Figure 1 illustrates the experimental procedure. Animals
were placed in the supine position and the bladder and pros-
tate were exposed through a midline abdominal incision.
Prostatic dissection and cavernous nerve isolation was carried
out with the rats in a supine position. The inferior hypogastric
plexus (ie, the pelvic plexus or major pelvic ganglia), pelvic
nerves, and cavernous nerve were identified posterolateral to
the prostate on both sides, and stainless-steel bipolar wire
electrodes were placed around these structures for electrical
stimulation. The penis was degloved, and both corpora caver-
nosa were exposed by removing part of the overlying ischio-
cavernous muscle. In order to monitor ICP, a 23-gauge can-
nula was filled with 250 U/mL of heparin solution, connected
to PE-50 tubing (Intramedi, Becton Dickinson), and inserted
into the right corpus cavernosum. Another 23-gauge cannula
was connected to a 1-mL syringe and inserted into the left
corpus cavernosum for intracavernous drug injection. Sys-
temic arterial blood pressure was monitored via a 25-gauge
cannula placed into the carotid artery (see Fig. 1).
Both pressure lines were connected to a pressure trans-
ducer, which was, in turn, connected via a Transducer ampli-
fier (ETH 400, CB Sciences) to a data acquisition board
(MacLab/8e, ADI Instruments). Real-time display and record-
ing of pressure measurements was performed on a Macintosh
computer (MacLab software V3.4, ADI); see Figure 1 for more
details. The pressure transducers and analog/digital (A/D)
board were calibrated in cm H2O before each experiment.

UROLOGY 51 (4), 1998 641

NEUROSTIMULATION PROTOCOL

KEY: CN 5 cavernous nerve; ICP 5 intracavernous pressure; IC 5 intracorporal; NC 5 no change observed as the corporal pressure was already higher than 70 cm H2O after IC papaverine and all changes are submerged under this pressure; SE 5 standard
Neurostimulation
of Distal (Cut)

(Mean 6 SE)

62.18 6 5.8

41.23 6 3.2
Nerve Ends
Direct electrostimulation of the cavernous nerve was per-
formed with a delicate stainless-steel bipolar hook electrode

NC
attached to the multijointed clamp. Each probe was 0.2 mm in
diameter; the two poles were 1 mm apart. Monophasic rectan-
gular pulses were delivered by a signal generator (custom
made, with a built-in constant current amplifier). Stimulation
parameters were as follows: frequency, 20 Hz; pulse width,
0.22 ms; duration, 1 minute; current, 1 mA. Before the exper-

(Drop in ICP)

(Mean 6 SE)
iment, cavernous nerves were cut and neurostimulation of the

Neurotomy

6 0.02

0.9 6 0.01
(cm H2O)
cut end of the nerve was performed.

NC
PHYSICAL MANIPULATION PROTOCOL

2
Direct physical pressure was applied by cotton tip swab to

TABLE I. Intracavernous pressure: response to dissection and papaverine injection

both sides of the prostate as well as the cavernous nerve.

Neurostimulation

113.54 6 10.83
of (intact) (CN)*

118.59 6 9.35

74.81 6 11.13
PHARMACOLOGIC PROTOCOL

(Mean 6 SE)
After completion of the neurostimulation protocol, a resting
period sufficient to ensure return of basal intracorporal pres-
sure was allowed (;15 to 30 minutes) prior to initiation of the
pharmacologic experiments. When basal intracorporal pres-
sure was achieved, papaverine (Eli Lilly) was injected into the
left crurum (corpus cavernosum) using a 23-gauge needle at-
tached to a syringe. Four bolus injections of papaverine (max-
imal injection volume of 60 mL) were administered to each rat

Nerve-Sparing
at half-log increments ranging from 100 to 3000 mg (ie, 100,

(Mean 6 SE)

1.32 6 0.49

1.13 6 0.15
Dissection
300, 1000, 3000 mg). The change in intracorporal pressure
was monitored with each dose, and all pressure responses

NC
were allowed to return to baseline before injection of the sub-
sequent dose lasting ;15 to 30 minutes in most cases.

STATISTICAL ANALYSES
All statistical analyses were performed using STAT-VIEW 4.5 Direct Pressure on
software (Abacus Concepts, Berkeley, Calif). The ANOVA test CN (Mean 6 SE)

52.51 6 6.37

37.88 6 9.38
was used for comparisons between experimental groups and
within each test group. Unless otherwise stated, all cavernous

* CN stimulation (1 mA) performed on right and left sides (observation multiplied by two times the number of rats).
NC
pressure data were expressed as the mean 6 standard error
(SE). Comparison between group means was accomplished
with a Scheffé multiple range test at significance levels of
P 5 0.05.

RESULTS
Stretching/Lateral
Displacement

INDUCTION OF DIABETES
30.31 6 4.31

19.31 6 3.32

There were 5 diabetic rats (urine glucose greater

of CN

NC

than 1000 mg/dL; blood glucose greater than 400

mg/dL) whose mean weight decreased from 234 to
198 g, consistent with results achieved in previous
studies.4 In control animals, the body weight rose
an average of 25% during the corresponding time
period.
13.18 6 1.392
(Mean 6 SE)

12.29 6 1.01

7.54 6 1.23
Basal ICP
(cm H2O)

FUNCTIONAL STUDIES
In normal rats (group 1), baseline cavernous
pressure ranged from 5 to 15 cm H2O (mean
12.29) (Table I). In diabetic rats (group 2), the
baseline pressure was significantly lower (mean
7.54). Nerve displacement by lateral or posterior
(1 IC papaverine)
Group 1 (n 5 10)

Group 3 (n 5 10)

movement caused the ICP to rise by approximately

Group 2 (n 5 5)
(diabetic rats)
(control rats)

30 cm H2O in control rats; in diabetic rats, the

error of the mean.

mean increase was 20 cm H2O. Electrostimulation

in normal rats (Fig. 2) resulted in intracavernous
pressure increases of approximately 10-fold from
baseline (;80% of systemic blood pressure), but of

642 UROLOGY 51 (4), 1998


FIGURE 2. Intracavernous pressures: response to elec-
trostimulation of intact cavernous nerve in control rats
(n 5 10). Intracavernous pressure in relation to neuro-
stimulation (1NS) with 0.5 to 10 mA of current, 20-Hz
pulse, 0.22-second duration, and to withdrawal (2NS)
of current.
FIGURE 3. Intracavernous pressures: response to elec-
trostimulation of intact cavernous nerve in diabetic rats
(n 5 5). Intracavernous pressure in relation to neuro-
stimulation (1NS) with 0.5 to 10 mA of current, 20-Hz
pulse, 0.22-second duration, and to withdrawal (2NS)
of current.
only sevenfold from baseline in diabetic rats (Fig.
3).
The ICP was not deflected from baseline appre-
ciably using nerve-sparing techniques during
periprostatic dissection. Neurotomy resulted in
measurable declines (;20% to 30% from baseline)
in intracavernous pressures in all rats. Papaverine
injections resulted in intracavernous pressure
change increases equal to those observed with elec-
trostimulation, but papaverine stimulation of the
cavernous body did not enhance sensitivity for ob-
UROLOGY 51 (4), 1998
servations of the effects of nerve displacement or
neurotomy (group 3). Electrostimulation of the
distal end of a severed nerve resulted in three- to
fivefold intracavernous pressure rise in all animals
(50% reduction as compared to intact nerve).
When electrostimulation was terminated, pressure
declined to 10% of baseline level within 2 minutes
and returned to baseline in 5 to 10 minutes in con-
trol rats. Intracavernous pressures in diabetic rats
declined more rapidly than in controls after termi-
nation of electrostimulation.
COMMENT
In 1982, Walsh and Donker1 described the
course and relations of the cavernous nerves in
stillborn fetuses. The autonomic branches of the
pelvic plexus, which lie in the dorsolateral,
periprostatic neurovascular bundle, are essential
for normal sexual function.5–7 The nerve-sparing
radical prostatectomy technique emphasizes the
need for direct visualization of these nerves; cur-
rently, it cannot be predicted at the time of surgery
whether the preserved nerves are functionally nor-
mal or if subsequent erectile dysfunction might be
a consequence of vascular damage.8 –10
Our investigation sought to characterize the
functional consequences of nerve displacement or
of nerve injury at the time of surgery in rats. Our
data show that the cavernous nerves can be stimu-
lated by tangential or lateral displacements, and
that these stimulations have measurable effects on
ICP, even in the absence of an observable erection.
Moreover, a careful, anatomic dissection to free the
cavernous nerves from their tenuous attachments
to the dorsolateral surface of the prostate can be
performed without demonstrable changes in intra-
cavernous pressure and with full preservation of
function. In rats there is a single cavernous nerve,
as opposed to man, in whom there are multiple
nerves, and anatomy is more complex but func-
tional aspects are the same.
In 1863, Eckhard11 described the phenomenon
of erections in animals following applications of an
electric current to their sacral nerve roots. Subse-
quent investigators learned to apply the current
selectively to specific nerve roots.12,13 Because of
the similarities between humans and rats with re-
spect to erections, the rat model has gained wide
acceptance.14 –20 In a previous investigation, we
showed that nerve-mediated erections, but not ex-
ogenous, pharmacologically induced erections,
were among the consequences of florid diabetes in
rats.20 In the current investigation, diabetic rats
consistently showed lower intracavernous pres-
sure increases in response to physical manipula-
tion, pharmacologic stimulation, and electro-
stimulation of cavernous nerve, and these data
643
support the observations of other investiga-
tors.21,22
Quinlan et al.23 showed that the immediate re-
pair of the cavernous nerve following injury re-
stored erectile function in the majority of rats
within 4 months of surgery. Similarly, Carrier et
al.24 demonstrated the possibility of nerve regener-
ation following neurotomy. Taken together with
our data, these studies suggest that the potential
clinical value of electrostimulation and intracav-
ernous pressure monitoring during radical prosta-
tectomy is threefold: first, the specific course and
relations of the cavernous nerves can be mapped
precisely prior to dissection; second, specific sites
of neurotomy can be identified; and third, preop-
erative erectile function (or dysfunction) can be
documented and used to guide postoperative sex-
ual rehabilitation, if needed. These types of clinical
investigations are ongoing at our institution.
REFERENCES
1. Walsh PC, and Donker PJ: Impotence following radical
prostatectomy: insight into etiology and prevention. J Urol
128: 492– 497, 1982.
2. Walsh PC, and Partin AW: Treatment of early stage
prostate cancer: radical prostatectomy. Imp Adv Oncol: 211–
223, 1994.
3. Apfel SC, Arezzo JC, Brownlee M, Federoff H, and
Kessler JA: Nerve growth factor administration protects
against experimental diabetic sensory neuropathy. Brain Res
634: 7–12, 1994.
4. Christ GJ, Valcic M, and Gondre MC: Augmentation in
the kinetic characteristics of phenylephrine- and 5-hydroxy-
tryptamine-induced contractions in the isolated rat aorta fol-
lowing eight weeks of STZ-diabetes. Life Sci 55: 807– 814,
1994.
5. Lue TF, Zeineh SJ, Schmidt RA, and Tanagho EA: Neu-
roanatomy of penile erection: its relevance to iatrogenic impo-
tence. J Urol 131: 273–280, 1984.
6. Lepor H, Gregerman M, Crosby R, Mostofi FK, and
Walsh PC: Precise localization of the autonomic nerves from
the pelvic plexus to the corpora cavernosa: a detailed anatom-
ical study of the adult male pelvis. J Urol 133: 207–212, 1985.
7. Breza J, Aboseif SR, Orvis BR, Lue TF, and Tanagho EA:
Detailed anatomy of penile neurovascular structures: surgical
significance. J Urol 141: 437– 443, 1989.
8. Aboseif S, Shinohara K, Breza J, Benard F, and Narayan
P: Role of penile vascular injury in erectile dysfunction after
radical prostatectomy. Br J Urol 73: 75– 82, 1994.
9. Bahnson RR, and Catalona WJ: Papaverine testing of
644
impotent patients following nerve-sparing radical prostatec-
tomy. J Urol 139: 773–774, 1988.
10. Lue TF, Gleason CA, Brock GB, Carroll PR, and Tana-
gho EA: Intraoperative electrostimulation of the cavernous
nerve: technique, results and limitations. J Urol 154: 1426 –
1428, 1995.
11. Eckhard C: Untersuchungen uber die Erektion des pe-
nis beim Hunde. Beitr Anat Physiol 3: 123–170, 1863.
12. Langley JN, and Anderson HK: The innervation of the
pelvic and adjoining viscera. J Physiol 19: 71–130, 1895.
13. Langley JN: On the regeneration of pre-ganglionic vis-
ceral nerve fibers. J Physiol (London) 22: 215–230, 1897.
14. Lesson TL, and Lesson R: The fine structure of the
cavernous tissue in the adult rat penis. Invest Urol 3: 144 –154,
1965.
15. Quinlan DM, Nelson RJ, Partin AW, Mostwin JL, and
Walsh PC: The rat as a model for the study of penile erection.
J Urol 141: 656 – 661, 1989.
16. Dail WG, Walton G, and Olmsted MP: Penile erection
in the rat: stimulation of the hypogastric nerve elicits increases
in penile pressure after chronic interruption of the sacral para-
sympathetic outflow. J Auton Nerv Sys 28: 251–257, 1989.
17. Fernandez E, Dail WG, Walton G, and Martinez G: The
vasculature of the rat penis: a scanning electron microscopic
and histologic study. Am J Anat 192: 307–318, 1991.
18. Chen KK, Chan JY, Chang LS, Chen MT, and Chan JH:
Intracavernous pressure as an Experimental index in a rat
model for the evaluation of penile erection. J Urol 147: 1124 –
1128, 1992.
19. Martinez-Pineiro L, Brock G, Trigo-Rocha F, Hsu GL,
Lue TF, and Tanagho EA: Rat model for the study of penile
erection: pharmacologic and electrical stimulation parame-
ters. Eur Urol 25: 62–70, 1994.
20. Rehman J, Chenven E, Brink P, Peterson B, Walcott B,
Wen YP, Melman A, and Christ G: Diminished neurogenic but
not pharmacological in the 2 to 3 month experimentally dia-
betic F-344 rat. Am J Physiol 272(Heart Circ Physiol 41):
H1960 –H1971, 1997.
21. Steers WD, Mackway-Gerardi AM, Ciamboui J, and De-
Groat WC: Alteration in neural pathways to the urinary blad-
der of the rat in response to streptozotocin-induced diabetes. J
Auton Nerv Sys 47: 83–94, 1994.
22. Bemelmans BL, Meuleman EJ, Doesburg WH, Noter-
mans SL, and Debruyne FM: Erectile dysfunction in diabetic
men: the neurological factor revisited. J Urol 151: 884 – 889,
1994.
23. Quinlan DM, Nelson RJ, and Walsh PC: Cavernous
nerve grafts restore erectile function in denervated rats. J Urol
145: 380 –383, 1991.
24. Carrier S, Zvara P, Nunes L, Kour NW, Rehman J, and
Lue TF: Regeneration of nitric oxide synthase-containing
nerves after cavernous nerve neurotomy in the rat. J Urol 153:
1722–1727, 1995.
UROLOGY 51 (4), 1998