Abstract
Chronic pelvic pain is a common condition that poses many unique challenges to health care workers. A careful patient history, physical exam, and appropriate imaging modalities are needed, necessitating an experienced practitioner. Clinical diagnosis is often clouded by a long differential diagnosis, which may present with similar signs and symptoms. A multidisciplinary approach with an extensive knowledge of physiology and anatomy are essential for successful treatment.
Depending on the etiology of disease, medical, interventional, or surgical treatment may be indicated. A stepwise approach moving through the interventional pain algorithm ( Fig. 31.1 ) is a safe and effective approach. How to treat pelvic pain can be quite controversial; often there is a lack of evidence for many of the proposed treatment modalities, which is reflected by the need for more research and the volume of trials currently ongoing.
Keywords
chronic pelvic pain, endometriosis, epidural steroid injections, pelvic floor pain, peripheral nerve blocks, trigger point injections
Chronic pelvic pain (CPP) is a major cause of morbidity and is defined as nonmenstrual-related pain below the umbilicus in men or women that has continued for greater than 6 months and creates a functional disability or requires long-term medical or interventional treatment.
CPP represents a different kind of pain, a different kind of patient, and a problem that is not necessarily straightforward or easy to fix. Due to the chronic nature of illness, the instigator for the pain may be gone but changes in the nervous system continue; thus, pain itself becomes the disease. It is the management of this pain faced by every pain physician that becomes the bulk of pelvic pain issues.
Epidemiology
CPP is an epidemic, and it represents approximately 2%–25% of the general population of women and is estimated to cost $881.5 million in the United States each year.
In the United States, primary care practices show a prevalence of one in seven women affected by some form of CPP. In one recent study by Jamieson, women of a reproductive age presenting to primary care practices with pelvic pain issues were shown to represent 39% of patients evaluated in that practice setting. Women in reproductive years in all settings were shown to represent 14.7%–24% of patients with the greatest incidence of pelvic pain found to be in women ages 26–30. Of all referrals to gynecologists, 10% are for pelvic pain. Of the 10% of gynecologic referrals, these patients are expected to undergo up to approximately 20% of hysterectomies and 40% of laparoscopies in the general population. The majority of women with chronic pain indicate chronic pain for 1–5 years, but CPP can be a life-long difficulty.
Although most pelvic pain concerns usually surround women, men also may be diagnosed with CPP issues. Most commonly, causes of CPP in men include chronic (nonbacterial) prostatitis, chronic orchalgia, and prostatodynia. Although men may have chronic pain issues from many disorders such as urinary dysfunction and irritable bowel syndrome (IBS), those listed above represent male-specific causes of pelvic pain. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a significant problem, accounting for 9% of all urological visits and 1% of primary care visits with 2 million office visits per year, which corresponds to a large health care burden to the United States. One study with a cohort of 51,529 men found 3.2% prevalence of CP/CPPS in men under the age of 50.
On an international level, a similar prevalence of CPP has been described in other countries regarding men and women. In the United Kingdom, incidence of CPP is similar to that of migraine, back pain, and asthma. These numbers extend to beyond medical conditions and personal consequences to pure economics. Epidemiologic studies show that CPP conditions affect the regular person and can seriously impact the day-to-day quality of life and quality of productivity in the workforce.
Demographics
In recently compiled clinical data from the Weill Cornell New York Presbyterian pelvic pain population, it has been shown that the majority of patients with pelvic pain are members of the working force: 22% are professional, 18% are clerical, 9% manual, and 4% are students. At the same time, it has been noted that 15% of working women between the ages of 18 and 50 reported time lost from paid work related to pelvic pain. In a breakdown of the social status of women affected with CPP at Weill Cornell New York Presbyterian, 48% of women are married, 23% are single, 9% divorced, 9% cohabitating, 4% separated, 2% widowed.
While similar data are not readily available for men, CPP has shown to be a significant psychosocial component. Patients commonly report decreased quality of life measures, depression, anxiety compared to spouses, and catastrophizing.
Cancer Pain
Patients with cancer represent a unique category of pelvic pain patients who deserve special consideration. They can suffer from pain related to tumor burden, radiation, chemotherapy, and surgery. They can experience pain from all available modalities including somatic, sympathetic, visceral, and neuropathic etiologies. Sympathetic and neuropathic pain symptoms are both less responsive to opioid therapy than nociceptive and visceral pain. Consequently, these patients become increasingly complex to treat.
In 1986, the World Health Organization (WHO) established a step-ladder approach specifically for cancer pain patients that revolutionized analgesic care for 70%–90% of patients with cancer pain. This approach emphasized a stepwise approach beginning with nonopioid agents and progression to stronger agents as indicated by patients’ clinical condition, with adjuvant agents incorporated including antidepressants, anticonvulsants, topical agents, nonsteroidal antiinflammatory drugs (NSAIDs), anxiolytics, and corticosteroids. Further approaches involved injection therapy, spinal anesthesia, neuroaugmentation, and more permanent, long-lasting neurolytic blocks. This category of patients will be mentioned only briefly, as the typical treatment pathway and goals of treatment are different for cancer patients and are often influenced by life expectancy, tolerance, and tumor growth.
Pelvic Pain Differential and Etiology
The diagnosis of CPP can be challenging, and 30%–50% of patients with CPP are classified as having “chronic pelvic pain without obvious pathology.” For example, referred pain patterns in CPP can be very difficult to identify even with experienced clinicians, and up to one-third of women who undergo diagnostic laparoscopy remain undiagnosed. Thus, a diagnosis and subsequent appropriate treatment is not always a straightforward algorithm.
When assessing the pelvic pain patient, it is important to approach these patients in a multidisciplinary fashion. Both diagnosis and management of these patients require good integration and knowledge of all pelvic organ systems and other systems including musculoskeletal, neurological, and psychiatric systems. A significant number of these patients may have various associated problems including bladder or bowel dysfunction, sexual dysfunction, and other systemic or constitutional symptoms. Other associated problems, such as depression, anxiety, and drug addiction, may also coexist.
Etiology
As CPP is an unclear diagnosis, pain can originate from any organ system and thus a thorough review of systems is essential to a proper assessment of a patient’s pain. These assessments can be organized in a system-based review and a gender-specific review ( Tables 31.1 and 31.2 ).
| Women | Men |
|---|---|
| Infection, endometriosis, dysmenorrhea (primary—menstruation, middleshmurtz, secondary—fibroids, adenolysis, IUD), dyspareunia, mononeuropathies, myofascial pain, vulvitis, cystitis, ovarian remnant syndrome, sympathetically mediated pain, pelvic congestion, pelvic fibrosis, pelvis neurodystonia, pelvagia, birthing pain | Prostatitis, chronic orchalgia, and prostatodynia, interstitial cystitis, ureteral obstruction |
| IBS and other GI disorders | IBS and other GI disorders |
| Sexual/physical abuse | Sexual/physical abuse |
| Cancer pain | Cancer pain |
| Psychiatric disorders | Psychiatric disorders |
| Surgical procedures (adhesions) | Surgical procedures (adhesions) |
| Reproductive | Visceral: uterus, ovaries, bladder, urethra Somatic: skin, vulva, clitoris, vaginal canal |
|---|---|
| Vascular | Dilated pelvic vein theory |
| Musculocutaneous | Ligamentous structures, muscular (iliopsoas, piriformis, quadrates lumborum, sacro-iliac joint, obturator internus, pubococcygeus) Skeletal (referred pain) from spinal lesions |
| Spinal | Degenerative joint disease, disk herniation, spondylosis, neoplasm of spinal cord/sacral nerve |
| Neurologic | Neuralgia/cutaneous nerve entrapment (surgical scar in the lower part of the abdomen), iliohypogastric, ilioinguinal, genitofemoral, lat femoral cutaneous nerves), shingles (herpes zoster infection), spine-related nerve compressions |
| Gastrointestinal | Irritable bowel syndrome, abdominal epilepsy, abdominal migraine, constipation |
| Urologic | Bladder dysfunction, chronic (nonbacterial) prostatitis, chronic orchalgia, and prostatodynia |
| Psychological (psychosocial/sexual) | Anxiety, depression, somatization, physical or sexual abuse, drug addiction, dependence, family problems, sexual dysfunction |
Theory
As shown by the broad differential of CPP, the pathophysiologic explanation of each disease is outside the scope of this chapter; however, below are some examples of well-known mechanisms.
Vascular Hypothesis
A vascular hypothesis, first postulated by Taylor in 1949 and more recently by Beard in 1984, may offer a clue into the mechanism of CPP. It has been noted that pain may be related to dilated pelvic veins in which blood flow is markedly reduced. Pelvic venous incompetence is likely seen in 10% of women, and up to 60% of patients with this abnormality develop pelvic congestion syndrome (PCS). These patients can find relief when the dilation is treated with foam sclerotherapy followed by coil embolization to within a centimeter of vein origin. Positive results have also been documented with medroxyprogesterone acetate therapy. Further studies by Foong in 2000 demonstrated that pelvic vein congestion shows a change in peripheral vascular reactivity that returned to normal after suppression of ovarian activity as compared to controls. Additional observation studies showed a reduction in pain for those patients whom congestion was diminished by hormonal therapy. It seems that some alteration of normal ovarian function was responsible for the observed changes in peripheral blood flow in response to a rise in venous pressure in women with pelvic congestion.
Alteration of Stimuli Processing or Organ Functioning
It has also been hypothesized that there is a rewiring of stimuli processing or a reorganization of organ function. A separate study by Rapkin in 1995 suggested an alteration in processing of stimuli by the spinal cord and further brain processing of stimuli could occur in women with CPP, a feature also shared by other chronic painful conditions. For example, undetected IBS presents in up to half of women referred for gynecological investigation. There is potential that visceral afferents may undergo a change in function similar to those of somatic nociceptors. This begs the question, does CPP represent complex regional painlike syndrome of the pelvis? Further research must be continued before conclusions can be made.
History and Physical Exam
There are many potential sources of CPP in all organ systems. A thorough history and physical exam are essential for assessment, diagnosis, and treatment of pelvic pain issues.
History
A history must be conducted consisting of a systematic review of systems-based assessments including gastrointestinal, skeletal, muscular, vascular, reproductive, urinary, neurologic, and psychiatric assessment ( Table 31.3 ).
| Pattern of onset Inciting event Quality (burning, aching, dull, sharp, cramping) Duration and progression of complaints Constant or intermittent nature Exacerbating factors (position, eating, urination, defecation, Valsalva) Alleviating factors | Efficacy and toxicity of previous medications Association with menstrual cycle Incontinence Pregnancy Sexual activity Sudden weight loss or weight gain Breast or endocrine difficulties Family history of ovarian, uterine, or breast cancer |
Physical Exam
A physical exam must be tuned towards the specific needs of the patient, specifically, the abdominal exam, pelvic exam, musculoskeletal exam, neurologic exam, and a psychiatric assessment. This review focuses on more in-depth musculoskeletal and neurologic evaluations with the understanding that the abdominal and pelvic examinations are components of any basic physical exam.
Abdominal Assessment
The focused abdominal exam is a core component of any physical exam and especially important in the assessment of pelvic pain. Auscultation for breath sounds, bruits, organomegaly, and palpations in four quadrants are all components of an abdominal exam.
Pelvic Assessment
A pelvic exam is an obvious component in the assessment of pelvic pain. An experienced physician should participate in a thorough examination of gynecologic, urologic, and overall pelvic health.
Musculoskeletal Assessment
All organ systems are important to assess, but, as per Baker in 1993, “musculoskeletal dysfunctions contribute to signs and symptoms of CPP and in many cases may be the primary factor.” In addition, “…coordination between the pelvic musculature and the pelvic visceral organs is essential for the proper functioning and integrity of the latter. The pelvic muscular element, which could well be the source of pain, must be evaluated.” Several maneuvers exist that can help identify pathology. A select few are listed as follows:
Trendelenburg sign: During single leg standing, the contralateral hip drops indicate hip muscle weakness. This may indicate gluteus medius or core muscle weakness.
Forced Faber test: Pain reported during abduction, flexion, and outward rotation of the hip while supine indicates pain originating from the pelvic girdle or hip joints. The examiner applies pressure to the knee and opposite anterior superior iliac spine during the maneuver.
Posterior pelvic pain provocation Test (P4 Test): Patients hip is flexed to 90 degrees while supine, a positive test in the ipsilateral hip, which is indicative of pain originating from the pelvic girdle or hip joints.
Pelvic floor muscle tenderness: Pain elicited during digital palpation of the lateral vaginal walls is indicative of myofascial pain.
Pelvic floor muscular strength: Positive test for weakness if patient is unable to lift and maintain contraction of the pelvic floor during a digital vaginal exam for at least 5 seconds is indicative of weakness of the internal pelvic core.
Pace maneuver: The patient abducts legs against resistance while seated is indicative of piriformis syndrome
Freiberg maneuver: With the patient supine, forcefully internally rotating the leg causing pain is indicative of priformis syndrome
It was found that examiners achieved 100% specificity in identification of CPP using pelvic floor muscle palpation and forced Faber test.
Neurologic Assessment
The neurologic exam is a natural counterpart to a thorough evaluation and differential of pelvic pain assessment. Below is a clearly stated chart that can allow the practitioner to conduct, assess, and interpret a good physical exam and its neurologic correlations in the lower thoracic, lumbar, and sacral regions (see Table 31.4 for neuromusculoskeletal examination).
| Muscle | Innervation | Referral Pattern | Symptoms |
|---|---|---|---|
| Iliopsoas | L1–L4 | Lower abdomen, groin, anterior thigh, low back, and lateral trunk | Pain with hip extension and weight-bearing, especially at heel strike |
| Piriformis | L5–S3 | Buttock, pelvic floor, and low back | Pain with standing, walking, and sitting |
| Quadratus lumborum | T12–L3 | Lower abdomen, anterior lateral trunk, anterior thigh, buttock, and sacro-iliac joint | Pain in lateral low back with standing and walking |
| Sacro-iliac joint | L4–S3 | Posterior thigh buttock, pelvic floor, low back | Pain with standing, walking, and a possible “catch” on one side with bending |
| Obturator internus | L3–S2 | Pelvic floor, buttock, posterior thigh, and coccyx | Includes “pressure” in pelvic floor |
| Pubococcygeus | S1–S4 | Pelvic floor, vagina, rectum, buttock | Pain in sitting, dyspareunia |
Psychiatric Assessment
An often overlooked but essential organ system is the psychiatric component of a patient’s physique. A good psychosocial or psychosexual history is needed when organic diseases are excluded or when coexisting psychiatric disorders are suggested. Sufficient history must be obtained to evaluate depression, anxiety disorder, somatization, physical or sexual abuse, drug abuse or dependence, and family problems, marital problems, or sexual problems. A high incidence of physical or sexual abuse is found in 30%–50% of patients with CPP of unknown etiology, and sexual abuse in patients before 15 years of age is associated with later development of CPP.
Modalities of Chronic Pelvic Pain
CPP is a common problem and presents a major challenge to health care providers because of its unclear etiology, complex natural history, and poor response to therapy. To treat patients effectively, the identification of the type of pain is absolutely necessary.
Nociceptive pain: Arises from stimulation of specific pain receptors that can respond to heat, cold, vibration, stretch, and chemical stimuli released from damaged cells and responds well to opioid treatment. An example would include pain experienced in an abrasion.
Somatic: Musculoskeletal system, sharp and well-localized pain, can often be reproduced; for example, pelvic floor dysfunction.
Visceral: Internal organs of main body cavities are usually dull and vague in location and radiating away from the affected organ. Chronic pancreatitis falls into this type.
Nonnociceptive pain: Arises from within the peripheral and central nervous system with no specific receptors existing. Pain is specifically generated by the nerve cell dysfunction and responds less to opioid, and more to antidepressants, anticonvulsants, N -methyl- d -aspartate (NMDA) antagonists, and topical capsaicin.
Neuropathic: From within nerve typified by hypersensitivity, tingling, numbness, weakness, burning, shooting. Diabetic neuropathy or lumbar radiculopathy are typical examples.
Sympathetic: Overactive sympathetic nervous system. Chronic regional pain syndrome is a prime example. In addition, pain mechanisms can overlap, and patients may present with complicated overlapping pain. Viscerosomatic convergence (referred pain from the viscera) is based on a principle that visceral innervations that converge terminally in the spinal cord at the same level as overlying somatic structures make it difficult to distinguish between somatic and visceral origins of “referred pain” (see Table 31.5 for categories of pain and their description).
TABLE 31.5
Types of Pain
Pain Category
Description
Nociceptive/somatic
Afferent A delta and C fibers
Nociceptive/visceral
Solid or hollow organs
Sympathetic
After a nerve or limb injury, diffuse burning, allodynia, hyperpathia, sudomotor dysfunction, impaired blood flow
Neuropathic
Sharp lancelike pain
Medical Treatment
As the causes of pelvic pain can be quite varied, the treatment modalities can also vary. Different genres of medications approach the treatment of pelvic pain using different mechanisms, and, in addition, combination therapy may provide synergistic analgesic options to contribute to the success of pain management control for another subset of the CPP population. As with any diagnosis and treatment in patient care, medical treatment must combine an art and science of medicine, as well as a balance of efficacy, and patient satisfaction, with appropriate side effect profiling.
Nonsteroidal Antiinflammatory Drugs
NSAIDs (i.e., ibuprofen and naproxen) have been frequently used for pain control in CPP. These medications inhibit the release of prostaglandins via cyclooxygenase (COX) inhibition, and have been implicated as inflammatory mediators in the pathophysiology of common etiologies of CPP such as dysmenorrhea and endometriosis. There are several consensus statements recommending their use as part of an empiric pain regimen, and they may also be useful at the initiation of a workup. Their use is limited by patient comorbidities, drug interactions, and contraindications. For example, NSAIDs should be avoided in patients with clotting or platelet dysfunction, peptic ulcer disease, or renal insufficiency.
Acetaminophen
Acetaminophen is an antipyretic with a central mechanism of analgesia. While it is reasonable to use with mild pain, there is a paucity evidence supporting its use in CPP, and support is largely anecdotal.
Opioids
Opioids are a common therapeutic modality in pain medicine; however, they have many side effects including nausea, vomiting, respiratory depression, tolerance, and a high potential for abuse. Opioids have little evidence for use in chronic pain. When possible, narcotics should be avoided and all other treatments should have been tried and failed. Opioids are likely to be beneficial for specific populations such as palliative and acute pain patients; thus, their discussion in this chapter is limited.
Oral Contraceptives, Gonadotropin-Releasing Hormone Analogues, Danazol
Oral contraceptives (OCPs) such as estrogen and progesterone or progesterone only are indicated for both birth control, hormonal regulation, and for CPP. OCPs address cyclic pelvic pain related to ovulation, endometriosis, and premenstrual dysphoric disorder (PMDD). By using hormonal regulation to block ovulation, these etiologies of CPP can be treated, especially in conjunction with NSAIDs; however, several studies have reported progestin alone can result in over 80% reduction or resolution of endometriosis-associated pain. OCPs may be advantageous given they can be continued indefinitely as opposed to most other hormonal interventions, and intrauterine devices (IUDs) have the added benefit of preserved bone density (with levonorgestrel in particular), a life span of up to 5 years, and a reduction in the regularity of menstruations.
Use of gonadotropin-releasing hormone (GnRH) analogues result in ovarian suppression and a hypoestrogenic environment for the endometrial stroma, thus inhibiting inflammatory cascades associated with endometrial proliferation. GnRH analogues have been studied regarding endometriosis, one of the most common etiologies of CPP. Benefit in reduction of symptoms when compared to danazol and OCP was similar. There are some findings that show if used in conjunction with aromatase inhibitors, efficacy is increased. GnRH analogues are still used as a second-line regimen due to side effects associated with ovarian suppression and higher incidence of CPP after termination of therapy.
Danazol is an oral androgen, a derivative of 19-nortestosterone. It decreases the release of gonadotropins from the pituitary, thus blunting the luteinizing hormone surge and preventing endometrial proliferation in a similar way to GnRH agonists. Additionally, danazol functions to increase circulating levels of testosterone, which can lead to undesirable side effects. GnRH analogues have largely replaced its use due to a more favorable side-effect profile. In addition, its use is not recommended beyond 6 months.
Antidepressants
The role of antidepressants has been well supported in the treatment of chronic pain. As with other medications used in CPP treatment, these agents provide not only analgesia, but other potential psychological mechanism for the treatment of chronic pain.
The analgesic effect of antidepressants are thought to be mediated by inhibition of serotonin (5HT) and norepinephrine (NE) reuptake, leading to increased tone of descending inhibitory spinal pathways with concomitant decrease in ascending nociceptive transmission. The pathophysiology behind these mechanisms is still not fully elucidated. It is unclear whether an increase in 5HT or NE is the dominant force behind analgesia. Recent studies show that tricyclic antidepressants (TCAs) and venlafaxine (a 5HT and NE reuptake inhibitor, serotonin–norepinephrine reuptake inhibitor [SNRI]) are equally efficacious; however, there is limited evidence for the efficacy of selective serotonin reuptake inhibitors (SSRIs). These agents may also augment effects of opioid analgesics. While research does exist showing the role of TCAs in neuropathic pain, there is a lack of research specifically demonstrating its role in CPP. Given that most of the research focuses on neuropathic pain rather than anatomic location or particular etiology, these findings are likely generalizable. The analgesic effect occurs in the absence of depression, at doses lower than those used for depression, and with an earlier onset (i.e., within one week) than that required for an antidepressant effect, suggesting that the mechanisms are different.
The following question has been raised: Is there a difference in the analgesic efficacy of antidepressants on the depressed versus the nondepressed population? Trials have addressed depression as a confounding factor through multiple studies. In fact, when using antidepressants for analgesic-oriented trials, depressed patients have been excluded and results have still shown a robust analgesic effect. On the other hand, trials that include depressed patients rarely, if ever, show a higher response rate in depressed patients. Analysis suggests that 50%–90% of the observed improvement in pain is due to a direct analgesic effect rather than an indirect effect of improving mood.
Multiple mechanisms may explain some overlap between chronic pain and depression. 5HT and NE play an important role in both disorders. For depression, drugs that act on 5HT or NE alone are equally effective. For pain, drugs using both 5HT and NE are superior to selective agents. A bidirectional relationship between chronic pain and depression does exist, and most evidence supports that chronic pain leads to depression. The latter plays little role in the responsiveness to pain processing and response to pharmacologic therapy. Tramadol and tapentadol, opioid agonists with 5HT and NE reuptake inhibition, respectively, show promise especially given the recent findings of monoamine systems in analgesia; however, these agents are too new to make formal recommendations.
Anticonvulsants
Originally synthesized in 1960 by chemist Walter Schindler in Basel, Switzerland, carbamazepine (CBZ) became the prototypic antiepileptic. It was first marketed as a drug to treat trigeminal neuralgia in 1962 and was later approved as an anticonvulsant in 1965. Noted similarities in the pathophysiology of epilepsy and neuropathic pain models justified the use of anticonvulsant drugs in the symptomatic management of neuropathic pain disorders as early as the 1960s.
CBZ changes the conductance of sodium ions. While evidence for its role in neuropathic pain exists, this agent has largely fallen out of favor for newer drugs with less severe side-effect profiles. The most recent systematic review on this topic has questioned the efficacy of CBZ in neuropathic pain.
More recently, the gamma-aminobutyric acid (GABA) analogues gabapentin (Neurontin) and pregabalin (Lyrica), which modulate voltage gated calcium channels, have been systematically reviewed and found to be effective for neuropathic pain. Gabapentin is well tolerated, easily titratable, has fewer interactions than CBZ, has a favorable side-effect profile, and is considered an excellent treatment for neuropathic pain. A study in 2005 provided a comparative prospective randomized controlled trial over 2 years, comparing gabapentin to amitriptyline and to combination therapy. Results from this trial showed that gabapentin alone or in combination with amitriptyline is better than amitriptyline alone in the treatment of female CPP using visual analogue scores as a primary outcome. This evidence has been reconfirmed in a recent Cochrane Review. Side effects were also lower in the group with anticonvulsants alone. New evidence posits gabapentin may have increased efficacy if used in conjunction with donepezil (Aricept).
Recently, a 2010 systematic review of anticonvulsant therapy does not indicate that anticonvulsants can be considered an evidence-based first-line therapy for pain syndromes outside of trigeminal neuralgia. Surprisingly, the Cochrane Collaboration recently retracted this article; however, the most recent version still upholds this conclusion. Anticonvulsant therapy may be appropriately withheld until other interventions have been tried.
Other anticonvulsant agents, for example, lamotrigine, oxcarbazepine, topiramate, lacosamide, clonazepam, phenytoin, and valproate, have also been investigated with little benefit noted.
Promising Therapies
Randomized controlled trials have been performed to evaluate the efficacy of other potential medical therapies in CPP. Overall, the literature is limited but promising with many new potential interventions on the horizon.
Ziconotide is an N-type calcium channel inhibitor derived from conotoxin, a peptide produced by the snail Conus Magnus. It is a novel agent that prevents the release of substance P and other nociceptive mediators. It was recently approved for intrathecal administration in the management of chronic pain. EMA401 is a competitive antagonist of the angiotensin 2 type 2 receptor, a site known to mediate nociception with a role in neuropathic pain. It is currently in phase II clinical trials for its role in chronic pain. The Na v 1.7 channel is a sodium channel known to be present in nociceptive neurons. They are not found in the myocardium or central nervous system (CNS); thus, their potential safety margin is much higher than traditional local anesthetics. In addition, several selective Na v 1.7 blockers are in phase II clinical development including funapide, raxatrigine, and ralfinamide. These agents show clear evidence of efficacy in chronic pain, and may have a role in CPP; however, this specific indication has yet to be explored.
Tanezumab is a monoclonal antibody directed against nerve growth factor developed as a pain adjunct. It has undergone phase II trials, specifically investigating its use in CPP conditions. One trial investigating its role in chronic abacterial prostatitis will need a larger population to demonstrate efficacy, but preliminary evidence is promising. A second study looking at interstitial cystitis was terminated early due to safety concerns; however, several phase III trials have been completed, showing its safety profile in patients with arthritis. This agent is an exciting possibility given its potential role specific to CPP.
Procedural Pain Medicine
Interventional Procedures
Procedures may be performed for diagnostic and therapeutic reasons. Unfortunately, diagnostic nerve blocks can be difficult to interpret as confounders are common. Thus, it is important to have a clear sense of the anatomical directed therapy used ( Table 31.6 ).
| Pelvic Organs | Spinal Innervation | Sympathetic and Peripheral Nerves |
|---|---|---|
| Fallopian tubes, superior portion of uterine segment, ureters and bladder, appendix, broad ligament, proximal large bowel | T9–T12, L1 | Celiac plexus, hypogastric plexus |
| Abdominal wall | T12–L1, L1–L2 | Ilioinguinal, genitofemoral |
| Inferior portion of uterine segment, ureters and bladder, superior vagina, distal colon, rectum, uterosacral ligaments | S2–S4 | Inferior hypogastric plexus, inguinal, genitofemoral |
| Lower vagina, vulva, perineum | S2–S4 | Ganglion of impar, pudendal, genitofemoral, inguinal |
Temporary but consistent responses to nerve blocks may lead to more permanent procedures such as pulsed radiofrequency neuromodulation or neurolytic nerve blocks if pain lasts. Usually, these more permanent procedures are indicated more towards cancer pain. A simplified version that can be used for directed interventional therapy is seen in the algorithm below ordered by level of invasiveness ( Fig. 31.1 ).
As with any intervention, it is essential that appropriate attention is given to safety and sterility and that a skilled support staff and appropriate monitoring and resuscitation equipment are available. The use of block needles, nerve location devices, and imaging (i.e., X-ray image intensifier, ultrasound, or computerized tomography) appropriate for the procedure is essential.
Trigger Point Injections
Myofacial pelvic pain (MFPP) is common and may contribute 14%–78% of the incidence of CPP. Trigger point injections show promise as effective techniques for myofascial pain: local anesthetics, saline, botulinum toxin A (botox), and even dry needling have been employed. Some applications include levator ani trigger point injections in CPP with positive results. Trigger point injections have also been tried in chronic prostatitis with promising results; however, the literature lacks power. Trigger point injections pose several challenges including success rates dependent on clinical experience, notoriously difficult referred pain patterns making physical diagnosis challenging, and MFPP being commonly overlooked by first-line health care providers. Additionally, trigger point interventions have also been associated with causing pain and voiding symptoms and a nidus for neurogenic bladder inflammation for patients with interstitial cystitis and urethral syndromes.
One particularly active area of researching utilizing trigger points is investigating botulinum toxin A. The role of Botox in health care is publicly known for its use in cosmetic medicine; however, Botox is also useful as an effective chronic pain medicine. For example, a pilot study demonstrated that Botox effectively treats CPP and associated spasm of pelvic floor muscles in women. Several meta-analyses have investigated its efficacy with some showing positive results, while the majority of meta-analyses report limited data and too much heterogeneity for formal recommendations. In a study comparing Botox and bupivacaine trigger point injections for myofascial pain treatment, both treatments had similar rates of success compared to placebo; however, it should be noted that bupivacaine remains a more cost-effective treatment. Currently, Botox remains an off-label use for the treatment of CPP; however, this indication is currently being assessed for US Food and Drug Administration (FDA) approval.
Epidural Steriod and Facet Joint Injections
Epidural steroid injections (ESI) and facet joint injections are targeted therapy procedures used as dermatomal-directed therapy, especially in radiculopathy. Caudal epidural interventions are particularly relevant in CPP. Similar to MFPP, radiculopathatic pain is often overlooked and confused with entities such as interstitial cystitis and urinary dysfunction. Evidence for the use of this modality lacks large-scale randomized controlled trials (RCTs); however, case studies and small RCTs do report its success. Larger studies are needed to increase the power of these conclusions, and similar injections with local anesthetic serve as powerful diagnostic tools if radiculopathic CPP is suspected.
Peripheral Nerve Blocks
As with epidural blocks and facet arthropathy, local anesthetic injections into peripheral nerves serve as a diagnostic tool for CPP by identifying the specific innervation. Nerve blocks are well described in the acute pain setting; however, their role in chronic pain is an active field of research that has only recently yielded positive results in major systematic reviews, and even so, most data on specific nerve blocks exists in smaller trials or case reports. Specific nerve blocks are listed below with evidence for suggested uses.
Ilioinguinal/iliohypogastric/genitofemoral blocks: May be useful in the management of CPP and have been described in the literature with respect to persistent postoperative pain, and perineal neuralgia.
Pudendal nerve blocks and infiltration: May be useful in the management of endometriosis, pelvic adhesions, pudendal neuralgia, and chronic prostatitis. There is a new generation of RCTs showing efficacy for this particular indication.
Caudal/sacral nerve: Caudal blocks have been known to be efficacious in interstitial cystitis. On the whole, local anesthetic injections into the caudal space have not been tested for CPP, and there is a lack of evidence for this indication to make formal recommendations.
Sympathetic Blocks and Neuroablation
Neuroablation of sympathetic nerves can be performed by using different techniques, including thermocoagulation (radiofrequency ablation), cryoablation, or injection of chemical agents (alcohol, hypertonic saline, phenol). There are several anatomical sympathetic sites with clinical relevance to CPP, namely, lumbar sympathetic, hypogastric plexus, and ganglion impar blocks. Hypogastric plexus can be subdivided into superior and inferior plexus. The superior plexus is located retroperitoneally at L3–S1 close to the sacrum and iliac vein bifurcation. The inferior hypogastric plexus is located in the presacral tissues ventral to S2–S4 vertebrae. The ganglion impar is located retroperitoneally where the lumbrosacral sympathetic chains end (slightly below the sacro-coccygeal junction) and supplies the distal-most structures of the pelvis. Lumbar sympathetic, hypogastric plexus, and ganglion impar blocks performed by a well-trained interventional pain physician may aid in the diagnosis and treatment of CPP. However, complications are possible and can lead to further painful dysfunction, including possible neuroma formation, neuritis, deafferentation pain, permanent motor and sensory losses, hypotension, diarrhea, sexual dysfunction, and incontinence.
Lumbar sympathetic blocks: May be helpful in the management of chronic cancer pain and possibly a range of pelvic pain conditions with afferents that pass via the L2–L4 levels; however, there is almost no literature regarding outcomes in CPP.
Superior Hypogastric Plexus Block
In 1990, Plancarte et al. showed that superior hypogastric plexus block (SHPB) provided a 70% decrease of pelvic pain in patients with cervical, prostate, or testicular cancer without complications. More recently, additional support for the technique was demonstrated in patients with cancer-related pelvic pain using a long-lasting neurolytic blockade that provided relief of pain in 69% of patients. Endometriosis and refractory penile pain have been evaluated, and percutaneous catheters have also been successful. SHPBs should be considered as an adjunctive therapy and not first line.
Inferior Hypogastric Plexus Block
Inferior hypogastric plexus block (IHPB) may offer analgesic overlap to areas not effectively covered by SHPBs. The inferior hypogastric plexus innervates the lower pelvic organs and has been shown to decrease CPP. Sahar et al. demonstrated markedly decreased opioid requirements and pain scores in cancer patients using a neuroablative block. This is a newer technique first described in 2007, and the community is just starting to investigate its efficacy in CPP.
Ganglion Impar Block
Ganglion impar blockade has been tested for several indications including CPP related to tenesmus, perineal pain, pelvic cancer pain, coccygodynia, and proctitis. For example, several case reports show successful use in treating coccygodynia and pelvic cancer. One RCT demonstrated its efficacy in chronic perineal pain; however, larger trials are needed. The large majority of the literature are case reports, and to our knowledge, no systematic reviews have been performed.
Neuromodulation and Spinal Cord Stimulation
Spinal cord stimulators (SCS) were approved in 1989 for their use in chronic pain. SCS are known to decrease average visual analogue scale (VAS) scores, disability indices, and opioid use. Efficacy has been validated by systematic reviews including use in CPP. Indications such as chronic regional pain syndrome (CRPS), radiculopathy, testicular pain, urge incontinence, urinary retention, interstitial cystitis, and cancer pain have been explored. This modality involves the placement of leads into the epidural space with electrical stimulation. Trial is on an outpatient basis with no surgery involved; thus, it is reversible. Those for whom trial stimulation is effective can consider more permanent implantation. While this is a minimally invasive procedure far down the pain algorithm, relatively high complication rates are reported (30%–40%), and while these are mostly minor complications, revisions and explanations can greatly affect cost and patient perception.
The best location for SCS lead placement underscores a recently debated topic. There have been several reports that high lead placement for CPP (as high as T6) may be more efficacious. A potential explanation for this effect may be that visceral pain fibers do not follow a dermatomal pattern and that higher placements may inhibit a greater proportion of these fibers. Specifically, sacral fibers entering the dorsal columns are medial relative to nerves entering rostrally. Since sacral fibers are the most medial nerves at any point of the dorsal column system, it follows that they can be stimulated at any point along their progression. Theoretically, the higher placement of electrodes would permit sacral stimulation as well as any missed fibers contributing to CPP above this level.
Neuromodulation
Neuromodulation for pain disorders and functional disease of the urinary tract have become a well-accepted concept. Pudendal nerve modulation is a technique that can be attempted when sacral nerve modulation fails; however, it is only practiced at a few institutions around the world, and only recently has standardization been published. There is a lack of large-scale trials evaluating the efficacy of sacral root modulation; however, several smaller studies exist. Most of these trials show significant and long-lasting effects from this treatment; however, larger clinical trials are needed.
Transcutaneous Electrical Nerve Stimulation
The transcutaneous electrical nerve stimulation (TENS) unit is a pulse generator with an amplifier and electrodes used to deliver continuous or varying duration of electrical nerve stimulation to relieve pain. The stimulation causes myelinated afferents to activate segmental inhibitory circuits with a cumulative effect. Induction time can be cumulative and typical recommendations include 30 minutes to 2 hours twice a day depending on the severity of the pain. Usually, the patient controls a modulated frequency between 0 and 100 Hz for pain control. A Cochrane review from 2008 looking at the effect of the TENS unit on chronic pain found no evidence for or against their use, which is a finding dually noted on several other meta-analyses. Additionally, it underlined that most of the studies are fraught with underpowered results and lack methodologic rigor; with almost none specifically looking at CPP. However, since that time, several RCTs investigating CPP have been published, which show dramatic improvement in pain scores and quality of life measures. The next major systematic review will likely shed more light on this topic.
Intrathecal Pump
Intrathecal pumps are last-line intervention after both medical and surgical interventions have failed. There are few studies available regarding CPP even though its use is widespread, and it is not a solution for the nonpalliative patient. Only three agents have been approved for this indication including morphine, baclofen, and ziconotide. Long-term use is associated with complications, namely infection (2.4%–7%) and granuloma formation.
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