Genitourinary Pain

General Features of Urogenital Pain

Pain localized to the lower abdominal, pelvic, groin, and/or perineal region can have multiple causes ranging from distortion of normal structures as a result of cancer to focal sites of inflammation and idiopathic systemic diseases. This type of pain falls within the practice of virtually every medical specialty but, in particular, the specialties of gynecology, urology, and gastroenterology. There are numerous common co-morbid conditions ( ), as well as similarities in manifestations and examination findings among the various urogenital disorders ( ). Perineal, groin, pelvic, and lower abdominal symptoms are some of the most common symptoms seen by primary care physicians. More than 50% of females experience urinary symptoms in their lives, and 15–20% have recurrent vulvar pain (childbirth excluded) at some point in life.

Pain experienced in the lower part of the abdomen, pelvic region, groin, and/or perineum may originate in the viscera but can also arise from pathology of the nervous system innervating these structures, vascular structures feeding these structures, or musculoskeletal–articular structures. Unlike pain arising from the surface of the body, which is well localized and evokes localized motor responses, deeper pain arising from most urogenital structures tends to have relatively poor localization and thus leads to ambiguity related to the origin of the pain. Such pain also tends to generate strong emotional responses, produce immobility coupled with tonic or “spastic” increases in muscle tone, and evoke vigorous, non-specific, autonomic responses such as changes in heart rate, sweating, and abnormal bowel or bladder control. Stimuli that predict real or potential tissue damage (e.g., cutting, burning, pinching) always produce reports of pain when applied to the skin but unreliably evoke reports of pain when applied to urogenital structures. Humans use tissue damage–related descriptors (e.g., stabbing) when describing their urogenital pain since a perception of tissue damage is present even if no tissue damage is occurring.

Organization of Urogenital Sensory Processing

The peripheral nervous system pathways related to urogenital structures in humans are complex and are summarized in Figures 54-1 and 54-2 by using the terminology of , who extrapolated from both human and non-human neuroanatomical studies. At first glance, one must wonder why such an elaborate intermixing of afferent and efferent pathways ever developed ( Figs. 54-3 and 54-4 ). Because of gonadal hormones and various other inhibitory factors and developmental cues, male and female urogenital structures differ markedly in both form and function. However, they share an innervation that follows the original location of the structural precursors during development. The testes and ovaries both descend from higher in the abdomen and carry with them a thoracic innervation. The urinary bladder, which arises from structures that traversed the developing umbilicus and that is still connected by the residual urachus, shares a similar innervation with sensory input extending up to the T10 level. Structures that physically open their orifices to sacral dermatomes all have dual spinal innervation consisting of both local sacral input (pelvic and pudendal nerves; S2–4) and thoracolumbar input that “reaches down” from these dorsal root ganglia (T10–L2) to travel with the efferent nerve fibers of the sympathetic nervous system through paravertebral ganglia (sympathetic chain). An apparent “gap” in the innervation of urogenital structures is simply the absence of these nerves associated with somites that selectively grew to be the hindlimb bud (L3–S1). Mixed with the spinal innervation are the wandering input and output of the vagus nerve and an elaborate local ganglionic circuitry. Conglomerations of ganglionic material have been lumped together by anatomists and named the pelvic (inferior hypogastric) and superior hypogastric ganglia or plexuses. Numerous additional names have been used, and pathways that traverse the celiac and superior mesenteric plexuses to high thoracic levels have been described extensively in other species. Furthermore, thoracolumbar afferents have been demonstrated to travel with sacral afferents via “contamination” of the pelvic nerve by input traversing the sympathetic chain. Simply put, the peripheral sensory innervation of urogenital structures is a web-like conglomerate of afferent nerves that travel by numerous paths through nerve plexuses in the pelvis and retroperitoneum and have their heaviest afferent input to the spinal cord at the T10–L2 and S2–4 spinal levels. Because of this plethora of pathways, an attempt to ablate all afferent input from urogenital structures by localized injections or radiofrequency treatments in the pelvis or retroperitoneal spaces is not a realistic goal, although a significant reduction in input from a specific structure can occur. Most afferents to the spinal cord have cell bodies located in the dorsal root ganglia, and hence peripheral ablation affects only axonal extensions of these neurons and spares cell bodies, which have a potential for regeneration.

The central nervous system pathways related to urogenital sensation have been roughly defined and include non-traditional pain pathways such as the dorsal columns of the spinal cord, but they also have components that follow the more traditional pathways of the anterolateral white matter (i.e., spinothalamic tract) of the spinal cord ( ). Clinical series have demonstrated effective treatment of urogenital (pelvic) cancer by dorsal midline ablation in humans ( ), but with only a few exceptions ( ), the effect of such lesions on chronic benign urogenital pain has yet to be demonstrated, and therefore identical pathways cannot be absolutely inferred. Known sites of tertiary-level supraspinal processing include the thalamus, hypothalamus, mesencephalon, pons, and medulla ( ). Cortical sites of urogenital sensory processing, inferred from positron emission tomography and functional magnetic resonance imaging (e.g., ), occur within the mid-cingulate cortex, bilaterally in the frontal and parietal regions, and in the cerebellum. Basic science studies of sensory processing in non-humans have demonstrated profound overlap of the sites and substrates of central nervous system processing for multiple urogenital structures (viscerovisceral convergence) and nearby somatic structures (viscerosomatic convergence).

Evocable Urogenital Sensations

Psychophysical studies in humans have examined some of the normal as well as abnormal sensations that are evoked by stimulation of urogenital structures. Cystometrograms (urodynamic testing) are commonly used in urological practice to evaluate urinary bladder sensation and function. In this procedure the bladder is slowly filled with fluid while intravesical pressure is measured and sensations evoked. A continuum of sensation is noted: fullness followed by an initial sense of urgency (need to void), followed by sensations of discomfort/pain and profound urgency ( ). Typically, during routine cystometrograms the bladder is filled until a predetermined maximal volume or pressure is reached or until subjects state that they can no longer tolerate the distending stimulus, and then the fluid is drained. Evidence of neurological dysfunction can be derived from either a hyperactive bladder or a flaccid, unresponsive bladder. Injuries can be central (spinal or supraspinal) or may involve peripheral nerves. Simple sympathectomy (to remove the sensory innervation traveling with the sympathetic fibers) does not abolish bladder sensation, but sympathectomy in addition to rhizotomy at the S2–4 levels or pelvic nerve section does lead to full loss of sensation produced by distention of the bladder ( ). Multiple repeated cystometrograms in normal healthy volunteers evoke an acute sensitization process, with progressively increasing sensory and reflex responses to urinary bladder distention being elicited by each subsequent cystometrogram ( ). Cardiovascular, respiratory, and visceromotor (abdominal contractions) responses to the distending stimulus were identified and measured in that and other studies ( ). Hypertensive crises can occur secondary to bladder distention and/or infections in subjects with spinal cord injuries (autonomic dysreflexia). Gastrointestinal structures have also been examined by using stimuli such as rectal distention, but formal discussion of this subject is deferred to Chapter 53 . Kidney pain has been studied by probing the pelvis of the kidney or distending the ureters and renal pelvis ( ). These stimuli produce pain and a secondary “spasm” of the flank musculature. Sympathectomy abolishes the renal pain. examined the secondary effects of ureteral stimulation produced by a kidney stone and quantified a lateralized sensitization of muscular structures on the symptomatic side with lowered thresholds for the production of pain by either mechanical probing or electrical stimulation of the flank musculature. This sensitization process may be magnified in the presence of other abdominal–pelvic pathology such as endometriosis ( ). Urethral “sensations” when passing urine have been noted by some investigators ( ), but formal psychophysical study of urethral sensation is lacking. Clinical observations of profound pain when passing urine in the presence of inflammation produced by infection such as gonorrhea suggest localization of sensations to either the bladder itself (females) or the penis and its tip (males).

Formal studies of pain evoked from female urogenital structures are limited. performed mechanical and thermal quantitative sensory testing of the vulva in 20 healthy women and compared these measures with similarly obtained ones in 22 subjects with a diagnosis of vulvar vestibulitis syndrome. Thermal pain thresholds occurred at a mean of 43.8°C in normal women and mechanical thresholds occurred at a mean of 158 mN on von Frey hair testing. This was in contrast to a thermal pain threshold of 38.6°C and a mechanical threshold of 14.3 mN in subjects with vulvar vestibulitis, thus suggesting the disorder to be an allodynia or hyperalgesia phenomenon. Similar secondary effects of “visceral” structure activation on the sensitivity of the abdominal skin and musculature to electrical stimuli were reported by in studies of females with and without the diagnosis of dysmenorrhea and in males. Menstrual cycle effects, sex differences, and a pain chronicity–related phenomenon were all noted.

In most males, it is all too apparent that pokes, prods, kicks, and compressive physical force applied to the testicles can evoke intense pain and profound autonomic responses. In a yet-to-be-reproduced study performed in 1933, the male investigators formally investigated this phenomenon in experiments on themselves. By applying known weights (50–1000 g) to plates that were compressing a testicle they noted that graded pain could be evoked. By selectively anesthetizing the various nerves traveling to the scrotum and its contents they were able to identify that purely testicular pain was localized to roughly the T10–L1 level and traveled via the superior spermatic nerve. Scrotal pain travels via the genitofemoral and branches of the pudendal nerves with localization to the groin/inner aspect of the thigh or sacral segmental levels. Formal psychophysical studies have not, to the best of our knowledge, been performed on other male genital structures, but clinical lore would indicate variable sensations ranging from pressure to pain, depending on the amount of pressure applied and the presence of inflammatory changes. Compression of the prostate on rectal examination can lead to a sense of urgency. The external male genitalia appear to have normal somatic sensory processing.

Evaluation of Urogenital Pain

Urogenital pain is a common symptom encountered by primary care clinicians. Initial evaluation includes an interview to assess the acute versus chronic nature of the complaints, exacerbating and ameliorating factors, and any co-existing disease. Chronic use of birth control formulations or medications that may affect bladder function is meaningful. Abdominal, rectal, and pelvic examinations can identify abdominal wall or pelvic floor rigidity or tenderness suggesting a peritoneal process or local musculoskeletal process. A distended bowel or bladder or underlying masses suggest possible neoplastic, infectious, or obstructive processes, and localizable tenderness may suggest a particular organ system. Direct visualization using a speculum may reveal visible pathology of the uterine cervix or vagina. Auscultation of bowel sounds may suggest the presence or absence of gastrointestinal motility and provide evidence of obstruction. Neurological examination may demonstrate evidence of neuropathy or localized radiculopathy. Basic laboratory examinations include testing for fecal blood, microbiological smears, urinalysis, blood cell count with white cell differential, electrolytes, and in some cases, hormonal measures. Radiographic evaluation, cystoscopy, urodynamic studies, or advanced imaging studies would be dependent on persistence or progression of the complaints. Spinal disease and associated nerve compression are often forgotten causes of urogenital symptoms despite established pathways for diagnosis and treatment ( ). As a consequence, imaging of the lumbosacral spine should be considered and evidence of compressive processes, such as those produced by disc disease or perineural (Tarlov) cysts, included in the differential diagnosis ( ).

Diagnostic evaluation of urogenital pain begins with the initial symptoms of pain, pressure, or discomfort associated with urogenital structures such as the bladder or vulva. A typical diagnostic bias is to first attempt to identify the pathologies that we believe we understand (cancer, infectious diseases, or anatomical abnormalities) because it is also our belief that we know the appropriate treatment of these pathologies. Often this is pragmatic since early identification of treatable pathology will change the course of care and may alter the outcome. For this reason, with any complaint of pain, cancer must be ruled out. In the absence of a history suggestive of a neoplastic process (e.g., weight loss) and unremarkable findings on physical examination, it is appropriate to focus on urogenital pathology by performing an “extended” physical examination through the use of methods such as cystoscopy, colonoscopy, hysteroscopy, or laparoscopy. When performing such visualization procedures, it is not uncommon for specimens to be taken for biopsy to rule out occult disease. These procedures often rule out the presence of any diverticula, stones, or benign tumors (structural abnormalities) that could be responsible for the symptoms. Evaluation for infectious diseases includes an assessment for sexually transmitted diseases (STDs), as well as tuberculosis, other bacterial or fungal infections, and specific viral infections such as genital herpes. A history of previous radiation treatment involving the pelvic region or chemotherapy known to produce secondary effects such as cystitis confuses the diagnostic process. Drugs such as tiaprofenic acid (a non-steroidal anti-inflammatory drug [NSAID]) may also produce a chemical cystitis, and hence ongoing pharmacological therapies (both prescribed and over the counter) must be evaluated as part of the patient’s history ( ). “Functional” evaluations such as urodynamic testing (cystometrograms) to evoke urgency or pain give information related to entities such as a neurogenic bladder, which may be hyperactive with involuntary bladder contractions (detrusor instability) or hyposensitive with elevated intravesical volume. Evidence of neurological dysfunction would suggest a neurogenic etiology. When the initial symptom is flank pain associated with blood in urine, it is necessary to consider cancer, infectious diseases, and anatomical abnormalities even though urolithiasis is likely. A similar diagnostic approach is used for testicular pain: cancer, infectious diseases, and anatomical abnormalities have to be ruled out by culture and focal imaging of scrotal contents. The pattern of evaluation is obviously recurrent: first rule out cancer, basic infectious diseases, and structural abnormalities and then perform more sophisticated examination of the painful area. Specific disorders will now be discussed with a more detailed description of their diagnostic findings plus potential therapies.