Dirk-Henrik Zermann, MD, Manabu Ishigooka, MD, Ragi Doggweiler, MD, Richard A.
University of Colorado Health Sciences Center, Denver.
[Infect Urol 12(3):84-88, 92, 1999. ]
Chronic abacterial prostatitis with associated pain remains a diagnostic and therapeutic challenge. Although the focus is most commonly a bacterial etiology, given the often unsuccessful results of antimicrobial therapy to relieve symptoms, it is reasonable to ask whether chronic pelvic pain syndrome may be a consequence of a functional disease within the pelvis. An analysis of clinical and urodynamic findings in 103 men with a complaint of chronic prostatitis-chronic pelvic pain was carried out with a neurourologic focus to evaluate the role of pelvic floor dysfunction as a cause of symptoms. All patients included in this study had negative microbiologic tests before entering the study group. A significant number of the men had neurologic dysfunction.
Men with pain in the genitourinary tract, a common problem, are generally given
a descriptive diagnosis such as orchialgia, chronic abacterial prostatitis, or
prostatodynia. The latter 2 terms have historically been used to classify
benign prostatic disorders. These classifications have helped to provide
guidelines for antibiotic therapy in prostatic diseases. However, these same
classifications have not adequately explained neurologic pain mechanisms or
defined potential therapies to relieve symptoms in men with pelvic pain
syndromes. Thus, the National Institutes of Health (NIH) recently redefined the
categories of prostatitis (Table I).
Male voiding dysfunction is often associated with discomfort or pain in the
suprapubic or perineal region, testes, tip of the penis, and low back area.
Neural dysregulation of the lower urinary tract could manifest as symptoms of
frequency and urgency.
Much of the research regarding prostatitis syndromes has centered around
microbiology as an etiology. Investigations have focused on cultures of
prostatic secretions and polymerase chain reaction to identify various
organisms responsible for inflammation in the prostate.[3-5] Most patients
continue to be treated with repeated antibiotic regimens without significant
In recent years, alpha-blockers, because they act on smooth muscle of the
bladder neck and prostate, have been found to be therapeutically useful in
prostatitis syndromes. Furthermore, investigations show a correlation
between symptoms of prostatitis and those of bladder dysfunction.[10,11]
Additionally, although infection is not a prerequisite for symptoms, it is
possible that the presence of an infectious organism results in an immune
reaction causing inflammation and subsequent pain and other symptoms.
Chronic prostatitis-chronic pelvic pain syndrome (CPPS) remains a diagnostic
and therapeutic enigma. Thus, other approaches have been utilized to explain
and treat this condition. A neurobehavioral perspective is emerging as a
plausible basis for diagnosing and treating some patients with CPPS. The
current study was conducted to evaluate voiding dysfunction and pelvic pain in
103 men through a retrospective review of symptoms, physical examination, and
Patients and Methods
Patients who had been treated at the University of Colorado Health Sciences
Center Clinic in Denver for voiding dysfunction and pelvic pain were the
subjects of this retrospective review. The clinic functions primarily as a
tertiary care center for patients referred with functional disorders of the
lower urinary tract. The clinic utilizes a standardized approach with all new
patients, including evaluating past medical history with a focus on previous
infection or inflammation, surgery, and traumatic events; documenting current
pain and dysfunctional voiding behavior; and evaluating other conditions that
are potentially related to somatic and autonomic dysregulation.
The clinical examination includes a neurourologic investigation that evaluates
the pelvic floor muscles via rectal examination. Voluntary contraction and, by
implication, control of the pelvic muscles are assessed. Urodynamic studies are
also performed. Sphincter function profiles (microtip catheter) are performed
in a staged fashion to record the reflex reactivity of the sphincter to light
touch. Sensation experienced by the patient to catheter withdrawal is noted.
Hypersensitivity is scored as none, mild, or significant. Basal sphincter tone
and behavior are recorded continuously during bladder filling and voiding by
keeping the pressure transducer within the external urethral sphincter region.
Overall pelvic floor activity is monitored via an intra-anal surface electrode
The urodynamic database includes a cystometrogram; uroflow measurement; and
measurement of sphincter sensitivity and closure pressures at rest and during
active filling; urethral functional length with a full and empty bladder; and
the ability of the patient to voluntarily contract and relax the sphincter with
a "hold" command.
All study patients had been screened with a urine analysis and culture to
exclude a microbiologic basis for symptoms, and cystoscopy or uroradiology to
exclude significant morphologic changes within the lower urinary tract.
Between August 1994 and August 1997, 103 patients with the main complaint of
pelvic pain of at least 12 months' duration were evaluated (Table II). All
patients had undergone extensive urologic and microbiologic evaluation -- as
well as several therapeutic attempts without relief of pain -- before being
seen at the clinic. All patients were considered to have NIH category IIIb
noninflammatory chronic pel-vic pain syndrome. The majority of patients had
pain within the perineum and testicular regions.
Findings from a total of 103 men (mean age, 47 years, range, 23-89) were
included in the review. The most common lower urinary tract symptoms reported
by patients included a slow, weak urinary stream (n=65) and hesitancy and
frequency (n=16). Incontinence (n=4) and retention (n=5) were rare. A small
percentage of patients reported headache (n=11) and bowel (n=8) and erectile
(n=6) dysfunction. One individual reported pain in both feet, the onset and
severity of which paralleled symptoms of dysfunctional voiding.
Four patients had a history of preexisting neurologic problems:
myelomeningocele (n=1), spinal cord malformation (n=2), and Persian Gulf
syndrome (n=1). A history of previous surgery was reported in 37 patients
(35.9%) (Table III), 25 of whom had no pain before surgery. In these cases,
pain began as a consequence of elective or accident-related surgery. Twelve
patients underwent surgery specifically to relieve pain (orchiectomy for
orchialgia, cystectomy for uncontrollable bladder pain) without success.
Evaluation of the pelvic floor via rectal examination revealed tenderness of
the striated muscle in 91 men (88.3%). This myofascial tenderness was always
associated with the inability to relax the pelvic floor efficiently either as a
single or repetitive effort. Follow-up evaluations confirmed these findings.
Although improvements were noted in some patients, rarely did these patients
learn to relax and control pelvic muscles.
Eighty-four patients (81.6%) underwent a urodynamic workup. The remaining 19
patients refused a urodynamic evaluation. The principal findings in nearly all
patients were: (1) hypersensitivity of the urethra or tenderness in the
external sphincter region, (2) a hypertonic sphincter, and (3) dyssynergic
behavior with voiding. These findings were scored individually to quantify the
degree of muscular dysfunction and hyperalgesia.
The average maximum bladder capacity was 395 mL. Cystometry showed abnormal
compliance in 5 patients. Normal compliance was evident in 95% of all patients.
Sphincter sensitivity, as evaluated by catheter insertion and movement within
the urethra during urethral evaluation, revealed that 10 patients had normal
sensitivity, 40 had minimally increased sensitivity, and 34 had markedly
increased sensitivity. This was scored using a linear analog scale.
The average functional sphincter length with an empty bladder was 45.7 mm
(range, 25-65 mm), and with a full bladder, it was 44.6 mm (range, 24-65 mm).
The urethral profile was normal in 12 men (11.7%); 44 (52.4%) showed a
dysfunctional/dyssynergic pattern, 10 (11.9%) had an obstructive behavior, and
18 (21.4%) had a combined functional and obstructive pattern. The average
urethral sphincter pressure was 81.9 cm H2O (range, 44-117 cm H2O) with the
bladder less than 50% filled and 93.6 cm H2O (range, 44-157 cm H2O) with the
bladder more than 50% filled.
Uroflow measurements revealed, in general, a decrease of maximum and average
uroflow. Peak uroflow was 14.4 mL/sec (range, 4-21 mL/sec; normal = >25
mL/sec). Average uroflow was 8.0 mL/sec (range, 2-15 mL/sec; normal = >11-13
Conventional approaches to diagnosis and treatment of chronic abacterial
prostatitis/CPPS have not adequately relieved the suffering of many men with
this condition. Clearly there is a need to investigate other factors that may
be involved in or contribute to the generation and maintenance of chronic pain
in the male pelvis.
The pelvic organs are uniquely linked to and organized by the nervous system,
involving sympathetic, parasympathetic, and somatic innervation. It has
been suggested that chronic nociceptive bombardment of central regulatory
(micturition) circuits via somatic (pelvic floor) afferents could trigger a
cascade of neural events, culminating in neurogenically mediated
inflammation. Function of the pelvic floor (striated muscle) directly
affects that of the pelvic viscera. It is not surprising, therefore, that
chronic pelvic floor dysfunction is often combined with smooth muscle
dysfunction of the lower urinary tract, and both may be maintained by
upregulated sacral reflexes.
A more complete understanding of the pathophysiologic relationship between
chronic pain and striated muscle behavior could lead to prevention and/or more
effective therapy for CPPS. Indeed, a review of these data showed that 92.2% of
men who presented to the tertiary care center for pelvic pain had dysfunction
of pelvic floor muscles. This finding was true regardless of evidence of
inflammation (prostatitis, cystitis). It should be noted, however, that this
patient population was a selected patient pool and therefore may not reflect
the typical patient with CPPS.
Many of these patients responded to modulation-based therapy, such as
biofeedback, alpha-blockers, or sacral nerve stimulation after failing
therapy with antibiotics and analgesics. This observation would suggest a role
for the nervous system in generating and maintaining symptoms of prostatitis
The central nervous system (CNS) is composed of a balanced (gated) circuitry
that appears to be predisposed toward neuronal instability (Fig. 1).
Disturbances of the CNS network may cause central dysfunction and dysfunction
of peripheral targets -- eg, the lower urinary tract. For example, the
relationship between dysfunctional muscle behavior and myalgia has been clearly
demonstrated for temporomandibular disorders. These relationships in turn
can create changes in central neural circuitry, with resultant permanent change
in the way in which nociceptive sensory information is processed (Fig. 2).
In the current study, 4 patients had a neurologic disease and pelvic pain. Even
if the pelvic floor dysfunction was secondary to neuropathology, the same
cascade of changed central processing could be initiated as in a "primary"
Surgical wounding, by its nature, involves an inflammatory reaction as a
necessary step toward healing. However, this process is also associated with
inappropriate afferent input to the spinal cord. It is known that a large
nociceptive barrage of afferent activity delivered to the CNS as a by-product
of surgical wounding can be destabilizing to neuronal circuits. This risk
increases if the neural regulatory pathways are already in a compromised
metabolic state. The mechanisms that determine excitability within CNS
circuits, hence the mechanisms that affect the modulation or processing of
information (afferent CNS input) on the cellular and molecular level within the
CNS, are only partly understood at this time. However, it is an accepted
principle that surgery can "wind up" central processing and initiate a chronic
pain state. Surgical wounding, as part of therapy, could aggravate symptoms
in the long term via these wind-up mechanisms.
Nearly 60% of the study patients had no significant medical history and no
apparent anatomic or medical cause that accounted for their chronic pelvic
pain. This finding, however, does not exclude the possibility that these
patients had a long-standing pelvic floor dysfunction. This could predispose
them over time to chronic pain and urinary tract dysfunction because of
compromised local immunity related to altered peptide pools (eg, substance P
presence or release).[20,21]
The pelvic organs share their innervation with the pelvic floor. Neurons at the
level of the spinal cord and the brain stem have broad functions to control and
modulate the activity of various pelvic organs. The flooding of nociceptive
afferent information (associated with dysfunctional activity within the pelvic
floor) into the brain stem nuclei could create a breakdown of normal gating
within these centers. A cascade of dysfunctional and autonomic symptoms could
Neuroanatomic studies using the retrograde transneuronal tracer
pseudorabies virus have shown a significant overlap of areas within the spinal
cord and the brain stem, which are involved in the innervation of perineal
muscles of the pelvic floor (ischiocavernosus muscle, bulbospongiosus
muscle), external urethral sphincter, urethra, and bladder.
Most of the spinal cord labeled neurons belong to areas representing the
sympathetic autonomic system. The labeled areas in the brain could be
considered to be directly connected with those in the spinal cord. However, it
should be emphasized that the premotor autonomic area in the hypothalamus and
ventrolateral medulla contains topographically segregated populations of
neurons that innervate individual sympathetic preganglionic functional units
and control specific patterns of their activity. The periventricular
nucleus of the hypothalamus serves as a "master control" for the autonomic
nervous system by providing highly specialized innervation to all autonomic
relay centers. Pain, once it is established, could be maintained via these
central sympathetic pathways.
This thinking is supported by concepts that have emerged from pain research.
Changes in central processing, expansion of receptor fields within the CNS, and
even cell death have been experimentally induced via noxious inputs to the
spinal cord. A compromise of brain stem regulation of micturition (and
other pelvic organs) may be possible based on current understanding of
neurophysiologic control for structures within the pelvis. The mechanisms
that allow for the overfacilitated and permissive communication within the cord
and brain stem are not clear, but would be similar to flawed inhibitory gating
observed in neuropathic states. This hypothesis is supported by improvement
rates of approximately 80% using therapeutic modalities that modulate the
pelvic floor function (eg, biofeedback, medication, sacral anterior root
stimulation). Spasticity of pelvic muscles could cause urine reflux into
prostatic ducts, causing inflammatory reactions. Thus, a neurophysiologic
perspective may contribute to our understanding of the pathophysiology of
clinical symptoms and supports a modulation-based therapeutic approach.
Given the association of muscle dysfunction and nociception, chronic pelvic
pain in some men could be considered a myofascial pain condition that is caused
and maintained by central neurogenic mechanisms. The observations reported, as
a whole, support the perspective that the bladder and urethral striated muscle,
when functionally compromised, are capable of triggering changes within the
CNS. These concepts regarding the origin of pelvic pain should be considered
when there is dysregulation of pelvic floor activity and traditional clinical
approaches fail to explain symptoms. This neurologic perspective requires a
more subtle diagnostic evaluation, but can shift emphasis of care toward
modulation-based treatments that "wind down" CNS excitability. Based on the
possible neuroregulation of CPPS, biofeedback and other modalities of
neuromodulation may improve symptoms.
Dr. Zermann is in the Department of Urology, University Hospital at
Friedrich-Schiller University in Jena, Germany. Dr. Ishigooka is in the
Department of Urology, Yamagata University, Yamagata, Japan. Dr. Doggweiler is
in the Department of Urology, University of Tennessee, Memphis. Dr. Schmidt is
Professor of Urology at the University of Colorado, Denver.
- Drach GW, Meares EM, Fair WR, Stamey TA. Classification of benign diseases
associated with prostatic pain: prostatitis or prostatodynia? J Urol.
- National Institutes of Health (NIH). Chronic Prostatitis Workshop. Bethesda,
Md: December 7-8, 1995.
- Pfau A: Prostatitis: a continuing enigma. Urol Clin North Am. 1986;13:695-715.
Krieger JN, Egan KJ. Comprehensive evaluation and treatment of 75 men referred
to chronic prostatitis clinic. Urology. 1991;38: 11-19.
- Shortliffe LMD, Sellers RG, Schachter J. The characterization of nonbacterial
prostatitis: search for an etiology. J Urol. 1992;148:1461-1466.
- Thin RN, Simmons PD. Review of results of four regimens for treatment of
chronic non-bacterial prostatitis. Br J Urol. 1983;55:519-521.
- Greenberg RN, Reilly PM, Luppen KL, et al. Chronic prostatitis: comments on
infectious etiologies and antimicrobial treatment. Prostate. 1985;6:445-448.
- DeLaRosette JJ, Humbregste MR, Meuleman EJH, et al. Diagnosis and treatment of
409 patients with prostatitis syndrome. Urology. 1993;41:301-307.
- Barbalias GA, Nikiforidis G, Liatsikos EN. Alpha-blockers for the treatment of
chronic prostatitis in combination with antibiotics. J Urol. 1998;159:883-887.
- Kaplan SA, Ikeguchi EF, Santarosa RP, et al. Etiology of voiding dysfunction in
men less than 50 years of age. Urology. 1996;47:836-839.
- Kaplan SA, Santarosa RP, D'Alisera PM, et al. Pseudodyssynergia (contraction of
the external sphincter during voiding) misdiagnosed as chronic nonbacterial
prostatitis and the role of biofeedback as a therapeutic option. J Urol.
- Hellstrom WJG, Schmidt RA, Lue TF, et al. Neuromuscular dysfunction in
nonbacterial prostatitis. Urology. 1987;30:183-188.
- JInemann KP, Lue TF, Schmidt RA, et al. Clinical significance and pudendal
nerve anatomy. J Urol. 1988;139:74-78.
- Mense S. Nociception from skeletal muscle in relation to clinical muscle pain.
Pain. 1993;54: 241-289.
- Food and Drug Administration. Gastroenterology and Urology Devices Panel.
Rockville, Md: August 6, 1997.
- Price DD, Mao J, Mayer DJ. Central consequences of persistent pain states. In:
Jensen TS, Turner JA, Wiesenfeld-Hallin Z, eds. Proceedings of the 8th World
Congress on Pain: Progress in Pain Research and Management. Seattle, Wash: IASP
- Svenson P. Pain mechanism in myogenous temporomandibular disorders. Pain Forum.
- Dubner R, Ruda MA. Activity-dependent neuronal plasticity following tissue
injury and inflammation. Trends Neurosci. 1992;15: 96-103.
- Coderre TJ, Katz J, Vaccarino AL, et al. Contribution of central
neuroplasticity to pathological pain: review of clinical and experimental
evidence. Pain. 1993;52:259-285.
- Birder LA, de Groat WC. Increased c-fos expression in spinal neurons after
irritation of the lower urinary tract in the rat. J Neurosci.
- Doyle CA, Palmer JA, Munglani R, et al. Molecular consequences of noxious
stimulation. In: Borsook D, ed. Molecular Neurobiology of Pain: Progress in
Pain Research and Management. Seattle, Wash: IASP Press; 1997:145-169.
- Kuypers HG, Ugolini G. Viruses as transneuronal tracers. Trends Neurosci. 1990;
- Marson L, McKenna KE. CNS cell groups involved in the control of the
ischiocavernosus and bulbospongiosus muscles: a transneuronal tracing study
using pseudorabies virus. J Comp Neurol. 1996;374:161-179.
- Nadelhaft I, Vera PL. Neurons in the rat brain and the spinal cord labeled
after pseudorabies virus injected into the external urethral sphincter. J Comp
- Vizzard MA, Erickson VL, Card JP, et al. Transneuronal labeling of neurons in
the adult rat brainstem and spinal cord after injection of pseudorabies virus
into the urethra. J Comp Neurol. 1995;355:629-640.
- Nadelhaft I, Vera PL, Card JP, et al: Central nervous system neurons labelled
following the injection of pseudorabies virus into the rat urinary bladder.
Neurosci Lett. 1992;143:271-274.
- Benarroch EE. The central autonomic network: functional organization,
dysfunction and perspective. Mayo Clin Proc. 1993;68:988-995.
- Swanson LW. The hypothalamus. In: Bj'>rklund A, H'>fkelt T, Swanson LW, eds.
Handbook of Chemical Neuroanatomy. Integrated Systems of the CNS. Amsterdam:
- McMahon SB, Wall PD. Receptive fields of lamina I projection cells move to
incorporate a nearby region of injury. Pain. 1984;19:235-247.
- de Groat WC, Steers WD. Autonomic regulation of the urinary bladder and sex
organs. In: Loewy AD, Spyer KM, eds. Central Regulation of Autonomic Functions.
New York, NY: Oxford University Press; 1990;310-333.
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