Obstetrician/gynecologists often are the initial management clinicians for pelvic neuropathic pain. Although treatment may require comprehensive team management and consultation with other specialists, there are a few critical and basic steps that can be performed during an office visit that offer the opportunity to improve quality of life significantly in this patient population. A key first step is a thorough clinical examination to map the pain site physically and to identify potentially involved nerves. Only limited evidence exists about how best to manage neuropathic pain; generally, a combination of surgical, manipulative, or pharmacologic methods should be considered. Experimental methods to characterize more precisely the nature of the nerve dysfunction exist to diagnose and treat neuropathic pain; however, additional scientific evidence is needed to recommend these options unanimously. In the meantime, an approach that was adopted from guidelines of the International Association for the Study of Pain has been tailored for gynecologic pain.
Modern obstetrics care obviously has progressed, with the addition of pain medicine to the management of labor, but application to gynecologic pain receives less attention. Neuropathic pain is defined as a pain arising as a direct consequence of a lesion or disease that affects the sensory component of the nervous system, according to the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain definition. Although there are no uniform definitions on magnitude and duration, this type of pain is severe (>5 on a 0-10 scale, with 10 being worst possible) and persists longer than superficial wounds (weeks to decades). Words used to describe the perception of neuropathic pain include “electric shock,” “dull,” “itching,” and “burning.” The challenge of exclusively confirming that pain is of neuropathic origin has led to the clinical guideline that it be graded as “definite,” “probable,” or “possible” neuropathic pain. Cardinal symptoms of neuropathic pain include hyperalgesia (increased sensitivity to pain) and allodynia (increased sensitivity to touch), although these are nonspecific. Although injured tissue is expected to recover after the resolution of the initial acute trauma, persistent changes in sensory processing (ie, spinal neuron responsiveness) can maintain a state of severe pain. Women, unfortunately, face many abdominal/pelvic insults that can cause probable neuropathic pain. Estimates of chronic pain after cesarean or vaginal delivery range from 10–20%; gynecologic procedures may be associated with a 5–32% risk. Plausibly, sex-dependent physiologic processes and neuroanatomic differences between women and men underlie the high risk of chronic pain after pelvic surgery; between-gender comparisons after surgical procedures generally suggest that women experience higher levels of perioperative pain, which likely reflects some component of neuropathic pain.
The study of pelvic neuropathic pain likely has been hampered by the wide and confusing differential diagnosis to consider abdominopelvic pain. Consequently, we will make recommendations for clinical practice that are based on more clear-cut disorders, such as diabetic neuropathy. One unique pelvic neuropathy is pudendal nerve dysfunction, which appears to result from the convergence of myofascial dysfunction and anatomic nerve compression between the sacrospinous and sacrotuberous ligaments. However, it too remains a challenge to characterize, because pudendal neuropathy is still not a discrete entity, but one that appears to be seen often with concomitant pelvic floor spasm.
The most important characteristic to recognize is that “neuropathic pain can be reliably detected using psychophysical clinical examination” rather than using other “diagnostic modalities (electrical, magnetic resonance, x-ray, etc) beyond the exam.” At the most peripheral edge, mechanical and chemical receptors on sensory fibers, termed nociceptors , convey electrical signals to the spinal cord that indicate the presence of a painful stimulus. Tissue is innervated differentially by multiple sensory fibers of varying sizes and properties, and different kinds of painful stimuli are processed by discrete sensory fiber types. Indeed, different kinds of trauma can produce damage to specific fiber types. Although deficits can be identified roughly by description, more precise characterization can be accomplished through quantitative sensory testing, which evaluates a patient’s pain response to pressure, electrical stimulation, or heat-/cold-evoked stimulation. We and others have applied these measures to characterize a limited subset of pelvic pain conditions that may have neuropathic components. Consistent with this idea, localization of the damaged nerve, combined with psychophysiologic characterization, represents a standard component of the diagnostic work-up for neuropathic pain, as will be described later.
The second most important principle in diagnosing neuropathic pain “is recognizing it often involves changes in central nervous system processing, not just peripheral tissues.” With central aberrations in pain modulation and processing, symptoms can be out of proportion to the degree of tissue insult and may not correspond to tight dermatomal distributions. In animal models, multiple studies show that a completely peripheral neuropathy (such as sciatic nerve ligation) is maintained by changes in supraspinal neurons. Stimulation of specific brain sites can provide profound analgesia and has spurred the development of brain-stimulation strategies for the alleviation of pain in patients with the most severe forms of pain. Corollary to this principle is that neuropathic pain affects sleep and disposition; therefore, therapies that improve quality of life from neuropathic pain must rectify brain-wide problems. Patients who exhibit evidence of central sensitization may need treatment with centrally acting neuromodulatory medications that are labeled for use as antidepressants, anticonvulsants, and sedative-hypnotics, despite the appearance of a peripheral problem. With these principles in mind, we describe the approach to the diagnosis and treatment of a few common pelvic neuropathic conditions.
Diagnosis
History
In practice, diagnosis of many cases of abdominopelvic neuropathic pain occurs predominantly after a recent surgical procedure. Inadvertent suture ligation, anatomic compression (even from benign sources, such as pants or girdles), and alterations in the perineural environment that are the result of metabolic changes (such as diabetes mellitus) have all been described in cases in which treatment of the presumed underlying issue resolved the patient’s symptoms. Outside of the perioperative period, gynecologists mainly will confront probable neuropathic pain in rare circumstances: when it appears to be endometriosis invading into pelvic nerves or spontaneous pain that involves compression of pelvic nerves (such as branches of the obturator, pudendal, or lateral femoral cutaneous nerves). In contrast, women with the more common fascial or distal extremity neuropathies should be referred to a neurologist for treatment. Superficial perineal pain (vulvodynia and pudendal neuralgia) has been suggested to be a neuropathic pain conditions as well; however, the research on nerve involvement is limited, and the exact mechanisms may be a combination of chronic mucosal inflammation and hormone or infection-mediated peripheral sensitization, rather than overt nerve disease.
If the pain occurs after a recent gynecologic procedure, the clinician should take a thorough surgical history, focusing particularly on previous transverse abdominal incisions (hysterectomies, inguinal herniorrhaphy, and appendectomies) that place the iliohypogastric, ilioinguinal, and genitofemoral nerves at risk. For perineal and deep pelvic/vaginal pain, both natural and operative vaginal delivery and vaginal prolapse and antiincontinence procedures (cystocele or rectocele repair, vaginal vault suspension, midurethral slings) are associated specifically with neuropathic pain in the pudendal nerve distribution. Widely used and validated questionnaires exist to screen for neuropathic pain conditions (such as the Leeds assessment of neuropathic symptoms and signs); however, the results should be paired with results from the clinical examination. Other questionnaires (such as the McGill Pain Inventory) can monitor progress and regression quantitatively. Inquiry about comorbid psychologic disturbances (mood, anxiety) should be performed in concert with a diagnosis of neuropathic pain, because it is well-established that neuropathic pain with disability is correlated with catastrophization.
Beyond sensory input, many of the pelvic nerves contain motor branches, and damage can impair certain functions. Assessment of bowel and bladder function, that includes incontinence, may reveal potential pudendal nerve dysfunction. Pain after defecation (several minutes to 1 hour) is a positive sign for pudendal neuralgia, according to the Nantes criteria ( Table 1 ).
| Inclusion criteria |
| Pain in the area innervated by the pudendal nerves that extends from anus to clitoris |
| Pain more severe when sitting |
| Pain does not awaken the patient from sleep |
| Pain with no objective sensory impairment |
| Pain relieved by diagnostic pudendal block |
| Complementary diagnostic criteria |
| Pain characteristics: burning, shooting, stabbing, numbing |
| Allodynia or hyperesthesia |
| Sensation of foreign body in the rectum or vagina (sympathalgia) |
| Pain progressively worse throughout the day |
| Pain predominantly unilateral |
| Pain triggered by defecation |
| Significant tenderness around ischial spine on vaginal or rectal examination |
| Abnormal neurophysiologic testing (pudendal nerve motor latency testing) in nulliparous women |
| Exclusion criteria |
| Pain located exclusively in the coccygeal, gluteal, pubic, or hypogastric area (without pain in the area of distribution of pudendal nerve) |
| Pruritus |
| Pain exclusively paroxysmal |
| Abnormality on the imaging test (magnetic resonance imaging, computed tomography, and others), which can account for the pain |
| Associated signs |
| Buttock pain (area around ischial tuberosity) with sitting |
| Referred sciatic pain |
| Pain referred to the medial side of the thigh |
| Suprapubic pain |
| Urinary frequency or pain with full bladder |
| Pain after orgasm |
| Dyspareunia or pain after intercourse |
| Normal pudendal nerve motor latency |
Clinical examination
A gynecologist at least can begin the initial workup of neuropathic pain with 2 simple tools: a wooden cotton swab and a dermatomal map of the abdominopelvic region. Clinical examination by testing the response to a light touch (such as a soft cotton swab) is the best initial test for identifying probable neuropathic pain. Sites where pain is produced by light touch should be documented as allodynic. Evaluation should begin with sites that are adjacent to where the pain is reported and then gradually move toward the site, because touch of the painful site can trigger allodynia in adjacent sites and obscure the diagnostic evaluation. Although gynecologists generally will limit their testing to response to mechanical sensitivity, neuropathy can also result in alterations in thermal sensitivity. Indeed, cold-induced pain can be tested by a drop of acetone on the suspected region, and visual analogue scores of ≥3 of 10 are considered possible evidence of neuropathic pain.
Beyond the general diagnosis of “neuropathic pain,” dermatopic mapping of pain is potentially useful for the specific identification of the affected nerve. The identification of sites with hyposensitivity after confirmed disc herniations has helped decipher the representation of the pelvic dermatome. The representation of the dermatome shown in the Figure may serve as a guide, but variation in the dermatome is known. Although this aspect of physical examination is not as familiar to many gynecologists, more frequent use would be in the best interest of patients. Indeed, a pelvic surgeon can provide the necessary comfort and expertise with pelvic/perineal examination to embolden a reluctant pain specialist or neurologist into performing a joint evaluation in more confusing cases.
With regard to pelvic neuropathic pain, injury to any peripheral nerve (eg, pudendal, genitofemoral, ilioinguinal) or plexus (eg, coccygeal, lumbar, hypogastric) may elicit sustained pain. The degree of spread into adjacent areas, or of spontaneous pain appearing in contralateral unprovoked sites, should be queried discretely. Evidence of autonomic abnormalities, such as erythema, or less commonly, sweating, may suggest central components to the pain and may point to a need for central agents to abolish pain successfully. Pins and needles–type sensation after compression over a suspected entrapped nerve is known as Tinel’s sign and may suggest local neural compression exists that may be amenable to surgical release. Abdominal wall nerves are involved commonly in abdominopelvic pain and the ilioinguinal (L1-L2), iliohypogastric (T12-L1), and genitofemoral nerve (L1-L2), all of which can be injured by compression or surgical ligation. Much anatomic variability exists with the course of the ilioinguinal nerve, but it can innervate the superomedial thigh, mons pubis, and labium majus. Pain in the abdominal region adjacent to the groin at the symphysis pubis and mons is suggestive of either genitofemoral or iliohypogastric involvement.
Pelvic and perineal peripheral branches likewise can be sources of pain. Pain that is exacerbated with sitting should direct assessment toward the perineal branches of the ilioinguinal, genitofemoral, pudendal, or lateral femoral cutaneous nerves (L2-L3). Recent diagnostic criteria have been proposed for perineal/pudendal nerve syndromes; however, these still require validation ( Table 1 ). The 2 divisions to consider are the posterior branches of the lateral femoral cutaneous nerve (L2-L3) and the pudendal nerve (S2-S4). Lateral femoral cutaneous nerve compression under the inguinal ligament can result in medial tight pain and over to the adjacent labium majus. The pudendal nerve dermatome extends over the labia, perineum, and anorectal region. Palpation transvaginally along Alcock’s canal, may reproduce the reported pain with pudendal involvement, although concomitant muscle or connective tissue dysfunction may also be present. Obturator nerve branches (L2-L4) supply mainly the medial thigh, but transobturator sling placement has been linked to both thigh and groin pain, which suggests variation in nerve distribution. Physical examination of the surrounding musculature, both at rest and during contraction (hip abduction/adduction and flexion/extension), can help in the localization of myofascial causes and is important to distinguish muscle spasm separately from neuropathic pain. Taut bands or trigger points are characteristic findings, that are more suggestive of myofascial involvement; trigger point injections with local anesthetic directly into the affected areas simultaneously can achieve diagnostic and therapeutic goals.
If lifting the patient’s leg 30-70 degrees while she is lying on the examination table induces pain (also known as Lasègue’s sign), this is a sign of lumbar or sacral herniation, with relatively high (approximately 90%) sensitivity. Evaluation of knee and ankle reflexes also is helpful to rule out lumbar disc herniation.
Testing
To enhance specificity, many experts routinely use diagnostic nerve blocks, particularly with readily accessible peripheral nerves, such as the ilioinguinal, the lateral femoral cutaneous, and the pudendal (by a transvaginal approach). How best to perform these blocks remains controversial because of the previously noted variability in pelvic dermatopic organization and the difficulty of precisely placing these agents into the correct plane, which leads some to suggest the use of ultrasound scanning or nerve stimulators.
Although gynecologic surgeons should gain comfort easily in performing abdominal or perineal nerve blocks, more sophisticated testing can be conducted by a neurologist. Modern quantitative sensory testing can apply precise thermal or electrical stimuli to characterize nerve-, electromyographic-, and cortical-evoked potentials that quantify and potentially localize the site of impairment. At present, its clinical utility remains uncertain, because its superiority to conventional bedside examination remains unproven. Although some widespread central pain conditions have demonstrated consistent deficits on quantitative sensory testing, future work is needed to validate its specific ability to evaluate nerve damage in pelvic pain conditions. Normative values for vaginal sensation have been determined that could allow for future comparisons, and impairments in tactile thresholds have been reported in women with suspected pudendal neuropathy. In the setting of comorbid visceral dysfunction, nerve conduction velocities can be used specifically to verify the existence of pudendal neuropathy-induced fecal incontinence. Decreased latencies are observed in pudendal nerve with idiopathic (neurogenic) fecal incontinence. However, generalizing results outside of specialty laboratories has proved to be an obstacle in the use of these techniques widely.
Treatment
All patients who experience chronic pelvic pain should be given benefits of comprehensive multimodal and multidisciplinary pain treatment, which refers to interventional nerve blocks; surgical interventions that include decompression of entrapped nerves; treatment with medication that has proved to have efficacy in treatment of neuropathic pain in general; physical therapy modalities; psychologic counseling and training; and treatment with complementary alternative medicine. In this review, we will focus on nerve blocks, decompressive surgical interventions, and medication management.
Neural blockade
Nerve blocks should be considered the first step in the management of a compressed nerve, because they can provide diagnostic information while providing acute pain relief. For many of the peripheral neuropathic pain disorders of the abdomen and pelvis, nerve blocks with the use of local anesthetic, with or without steroids, are used to reduce the spontaneous ectopic activity of the involved nerve. Particularly for presumed pudendal nerve pain and vulvar pain, a series of monthly local anesthetic blocks have reduced symptoms in small, uncontrolled studies.
Although high-quality evidence is limited, many clinicians view a clinically meaningful degree of improvement (as interpreted by the patient to persist approximately 2-4 hours, depending on which anesthetic is used) after a block to warrant a series of repeated blocks. An interval separated by a few weeks to a month generally is accepted. The occasional patient will experience dramatic, prolonged reduction of symptoms. In the original study by Arner et al, 18 of 38 patients experienced relief that exceeded 12 hours after each bupivacaine block. These patients had a wide variety of mononeuropathies that were distributed across different segmental dermatomes. The exact agent, volume, and whether to use ultrasound guidance or a nerve stimulator to guide the block remain unresolved questions. Typically, in the office, we inject either bupivacaine 0.25% or lidocaine 1%, buffered with sodium bicarbonate, and place a total of 2-3 mL with a 25-gauge needle into the path of the involved nerve. In particular with pudendal neuropathy, some practitioners prefer a computed tomographic–guided approach transgluteally vs the classic obstetric transvaginal injection approach medial to the ischial spine, but evidence is predominantly anecdotal and limited to a select group of specialized centers globally. Beyond treatment, blocks have been taken for granted to represent an effective prognosticator of surgical outcome for decades. Nevertheless, it has been demonstrated recently that pain scores after diagnostic nerve block predict outcome after the surgical management of neuroma. Therefore, the use of neural blocks and subsequent results should be considered seriously before an attempt at higher risk interventions if a discrete lesion is suspected.
Decompressive and surgical interventions
When an acute mononeuropathy is suspected, aggressive decompressive efforts by physical therapy or surgery may be the most ideal treatment after conservative approaches have failed. In the ideal setting, an anatomic cause for neuropathic pain can be identified and reversed. Sadly, the published literature is sparse with reports of treatment of such conditions after pelvic surgery. Nevertheless, several case reports warrant mention. The best example is acute ilioinguinal or iliohypogastric nerve entrapment after fascial closure of abdominal wall incisions, such as with inguinal herniorrhaphy, Pfannenstiel incisions, or even lateral endoscopic port closure. In the past year we have seen 2 cases of acute unilateral ilioinguinal nerve entrapment after routine laparoscopy that resolved within a week of the initial surgery after the removal of the fascial stitches. Both cases did not respond to an aggressive initial attempt at nonsurgical medical management. Similar relief has been described with the release of an entrapped branch of the pudendal nerve a year after cystocele surgery in 2 patients who potentially had lumbosacral nerve roots that were compromised at the time of uterosacral vault suspension that responded to prompt suture removal within 2 weeks of the original surgery. How long to wait before an attempt at surgical release of an acutely entrapped nerve is largely unknown. Many cases clearly do resolve with observation and pain control, and clearly, a dialogue with the patient will guide how quickly this decision is made.
The surgical management of pudendal neuropathic pain deserves separate mention. Surgical decompression of the nerve aims to free it from a compressed position between the sacrospinous and sacrotuberous ligament. The predominant approaches have been described through either the transgluteal or transischiorectal fossa by 2 separate French teams. Robert et al have published a small, unblinded, controlled trial that mirrors their larger general experience with several hundred patients that suggests that 70% of patients will report improvement, but up to 30% of cases will report unchanged or worsened perineal pain. Patient selection is critical, so these teams generally have reserved surgical treatment to those patients who have a partial response to initial conservative measures (such as avoiding sitting and a series of nerve blocks into the pudendal distribution).
These small studies suggest that prompt recognition and release of potential nerve entrapment after surgery can be effective but that further research is needed. Particularly for pudendal nerve release surgery, referral to a specialist may be the best approach, given the limited experience most gynecologists will have with these surgical approaches. Unfortunately, failure rates and improvement over conservative management for these revision procedures are unknown, based on the lack of comparative studies with any significant long-term follow-up data. Similarly, small case studies have suggested that abdominal wall or retroperitoneal ligation of injured ilioinguinal, iliohypogastric, or genitofemoral nerves can be effective when a release is not feasible. An important caveat is that, in a subset of patients, ligation can produce sustained deafferentation pain, which can be equally if not more devastating.
In specialty pain clinics, a variety of more aggressive interventions have been described to attempt to alter aberrant pain processing at all potential targets of the neuraxis, which include radiofrequency ablation of peripheral nerves, lumbar sympathectomy, or stimulation of the peripheral nerve, spinal cord, brainstem, or cerebral cortex. Unfortunately, adequately powered, pelvic pain–specific, randomized, controlled trials are generally lacking, and extrapolation from a small number of case series to general practice is risky, given the wide potential for adverse outcomes when neural structures that are involved in critical homeostatic processes are targeted. Given the risk profile, we would suggest to most practicing gynecologists that, when nerve blocks and straightforward surgical revision are not an option or do not prove effective, patients should be expeditiously offered a combination of medical and alternative strategies to achieve symptom control before choosing more drastic measures.
Medical management
Pharmacological therapy is used frequently for neuropathic pain, although the specific data for pelvic pain disorders are also quite limited. Unfortunately, only approximately one-half of patients experience clinical relief in randomized trials of medications, and frequently, it is only partial relief. The classic diabetic polyneuropathy and postherpetic mononeuropathies are treated generally with tricyclic antidepressants or atypical antidepressants and anticonvulsants. The exact mechanisms by which these drugs provide pain relief are not understood entirely but, in part, likely involves the modulation of neuronal hypersensitivity. Of note, multiple, randomized, controlled trials have shown that lamotrigine, an anticonvulsant, does not appear to be effective for a number of neuropathic pain conditions. Still, gynecologists should be comfortable prescribing these medications, as long as they educate patients about the potential central nervous system side-effects, which generally resolve with withdrawal of the medicine ( Table 2 ).
