New Directions in the Treatment of Pelvic Pain

Mercy A. Udoji, Udoji MA, Timothy J. Ness
Pain management · 2013 · vol. 3(5) , pp. 387–394 · doi:10.2217/pmt.13.40 · PMID:24654872 · PMC3979473 · W2149714618
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This review examines current and novel therapeutic options for chronic pelvic pain, including neuromodulation, pharmacology, and complementary medicine, alongside focal therapies and empiric treatments.

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This review article examines the complex etiology and multifactorial nature of chronic pelvic pain, highlighting its diverse origins in gynecologic, urologic, gastrointestinal, and musculoskeletal systems. It explores emerging basic science findings regarding genetic polymorphisms, epigenetic mechanisms, and neurophysiological pathways such as central sensitization and visceral cross-talk that contribute to pain perception. The authors discuss novel therapeutic targets identified in preclinical trials and advocate for a multidisciplinary management strategy using tools like the UPOINT system alongside neuromodulation techniques. Relevance to endometriosis: endometriosis is cited as one of several gynecologic causes of chronic pelvic pain and is referenced in the context of experimental models for studying hyperalgesia and epigenetic modulation.

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Abstract

SUMMARY The treatment of chronic pelvic pain in both females and males is a challenge for pain clinicians. Standard therapies are multimodal in nature with use of behavioral, medical and procedural therapeutics. In recent years, our understanding of the neurobiology of this disorder has improved and novel approaches have focused on neuromodulatory options, novel pharmacology and complementary/alternative medicine options. This review briefly examines newly employed therapeutic options, while restating currently utilized options. The current state-of-the-art treatment includes focal therapies for identified pathologies and empiric trials of other options for care when precise sources of the chronic pelvic pain are ill defined.
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New

Physical therapy, dietary therapy and complementary and alternative medicines are useful adjuvants to traditional therapies. Physical therapy utilizing myofascial release techniques and pelvic floor muscle exercises is regularly used in multimodal treatment plans. Fitzgerald et al. determined the feasibility of performing a randomized clinical trial comparing two types of physical therapy for patients with urologic CPP. Their results were notable for a better response in patients managed with myofascial physical therapy as opposed to global therapeutic massage [ 43 ]. In 2011, a randomized clinical trial evaluated the efficacy of yoga in relieving the pain of patients with known primary dysmenorrhea. Its results indicated that the performance of yoga poses during menses (cobra, cat and fish poses) were associated with significant decrease in pain duration and intensity compared with the control [ 44 ]. If these results are borne out, a similar technique could be applied to the treatment of patients with CPP. Acupuncture has grown in popularity and is now used to manage a variety of pain disorders, as well as postoperative nausea and vomiting. Regarding acupuncture and CPP, reports about the successful use of acupuncture or acupuncture with electrical stimulation pepper the literature and in general they have been positive, with significant decreases in pain scores over placebo noted in a majority of the studies [ 33 , 45 , 46 ]. Dietary therapy is based on evidence that a higher intake of fresh fruit and vegetables containing high amounts of antioxidants is associated with increased immune function and decreased free radical/oxidative stress to the body. This therapy recommends increasing the patient's intake of natural inhibitors of COX function (vitamins and n-3 fatty acids). These serve to boost the body's natural ability to fight free radicals and reduce pain via a reduction in prostaglandin and inflammatory cytokine production [ 47 ]. It should be noted that work in this arena has been largely experimental. Twice-daily use of quercetin (a red wine/green tea extract) was shown to improve male CPP in double-blind, placebo-controlled trials [ 48 ]. In murine models, there is ongoing research to evaluate epigallocatechin-3-gallate, a component of green tea that is thought to be responsible for its antiangiogenic, antioxidant and anti proliferative effects; and reservatrol, found on grape skin, responsible for antioxidant and anti-inflammatory effects of red wine. The authors tested these agents by transplanting endometriosis-like lesions into mice and randomized the animals to receive reservatrol or epigallo catechin-3-gallate. Their results showed significant suppression of the development of endometriosis lesions in treated mice in both groups, but the epigallocatechin-3-gallate group showed a greater degree of suppression of these lesions compared with the reservatrol group [ 49 ].

Current

Since evidence-based management options for CPP with and without defined pathology are limited, as few therapeutics have ‘proven’ clinical efficacy, a multidisciplinary approach to the treatment of these patients is essential ( Table 2 ) . Frequently, the diagnosis assigned to a painful condition is dependent on the initial specialist who evaluated the patient: urologists assign urological diagnoses; gynecologists assign gynecological diagnoses. A prudent approach for any pain clinician is to take a fresh look at existent evaluations and to assess the multiple etiologies that are possible, but not considered. A phenotypic approach championed by Nickel et al. and Shoakes et al. is the UPOINT system, which has six domains: urinary, psychosocial, organ-specific, infection, neurologic/systemic and muscle tenderness [ 22 , 23 ]. These domains define potential lines of diagnostic investigation and suggest treatment options in relation to urogenital pain, thereby giving some structure to their clinical approach. The UPOINT approach has been extended and modified by some international organizations to the broader category of pelvic pain [ 24 ] and appears to be a valid initial approach to a patient's pain complaints. If the underlying cause of the pain is defined, then subsequent treatment is centered on that particular etiology, otherwise a more global ‘empiric’ approach must be taken. Diagnostic laparoscopy, lysis of adhesions and exploratory laparotomy are the most common procedures performed in this population of patients. Medication management also plays a vital role. Opiates, muscle relaxants, antidepressants and anticonvulsants have all been used with varying efficacy. In recent years, interventional techniques have moved to the forefront as management has shifted away from invasive surgical exploration to minimally invasive and percutaneous procedures. Focal local anesthetic and depot steroid injections at neuraxial and peripheral sites have been commonly employed. The successful use of neuromodulation (including spinal cord and posterior tibial nerve stimulators) and radio frequency thermocoagulation has been well documented in published literature [ 25 , 26 ]. Adjuvant techniques, including biofeedback, acupuncture and massage, are used as part of a true multimodal treatment approach.

Overview

Chronic pelvic pain (CPP) is most commonly defined as continuous or intermittent pain that occurs in the lower abdomen or pelvic area that is cyclical or noncyclical in nature, and causes functional limitation in activities of daily living or reduced quality of life [ 1 ]. CPP is more prevalent in females, with an estimated worldwide prevalence of 2.1–24%. The annual cost to the USA's health system has been reported to be greater than US$800 million. Up to two-thirds of patients with CPP do not carry a definitive diagnosis [ 1 , 2 ]. The emotional toll on the patient, family and healthcare providers is immeasurable, as all parties involved become frustrated by the lack of progress that is common in the management of this disorder. The signs and symptoms of CPP vary from patient to patient with regards to location and intensity, as well as presence or absence of associated urinary symptoms and sexual dysfunction. To further confound the issue, innervation of the pelvis is complex, making diagnosis of pain originating in this region of the body very difficult [ 1 ]. In addition to a thorough history and physical examination, careful utilization of laboratory and imaging studies should be used to help make the appropriate diagnosis. The etiology of CPP is multifactorial and its pathophysiology is complex and incompletely understood [ 1 ]. CPP can arise from a multitude of causes in various organ systems, including gastrointestinal (e.g., inflammatory bowel disease and irritable bowel syndrome), neurologic (nerve entrapment and disc herniation), gynecologic (e.g., endometriosis and pelvic inflammatory disease), urologic (e.g., bladder pain syndrome and prostatitis) and musculoskeletal (e.g., sacroiliac joint dysfunction and symphysis pubis dysfunction) ( Table 1 ) [ 2 ]. Coexisting painful disorders may be present and serve to enhance the overall pain symptoms through mechanisms of cross-organ sensitization resulting in viscero–visceral or viscerosomatic hyper-algesia [ 3 ]. Treatment of defined disorders follows typical treatment pathways with the use of anti-inflammatory therapies (focal or systemic) when inflammation is identified and the use of neuropathic pain medications when clear pathology is identified within local neurological structures. In many cases, the precise pathology is not identified. In these instances, pathophysiologic theories suggest that CPP may be a result of abnormal CNS responses that maintain the perception of pain in the absence of acute injury [ 4 ], taking the features of a subtype of complex regional pain syndrome [ 5 ], or more simply as ‘central sensitization’ of the CNS with a decrease in pain thresholds and increase in normal pain intensities [ 6 ]. Since CPP often has mixed elements of neuropathic pain, inflammation and complex regional pain syndrome, patients may respond favorably to central acting medications, as well as stimulation of the CNS and peripheral nervous system.

Conclusion

CPP is a complex disorder whose prevalence in the general population is comparable to asthma, chronic back pain or migraine headaches [ 50 ]. With poorly understood etiology and pathophysiology, management of this disorder mandates the use of a multidisciplinary approach. There are a variety of interventional, surgical, and medical and alternative approaches available to treat this disorder; however, none of them have been proven to be consistently effective and so novel therapies such as those presented in this report have been employed. The current state-of-the-art treatment for CPP often involves a trial and error approach in order to attain the best results for any individual patient. Research on this disorder is extensive and ongoing. The use of neuromodulatory/neurostimulatory methods presents significant potential for interventions related to pain that is unresponsive to more traditional medical and behavioral therapies. Hopefully, within the next 5–10 years, sufficient well-controlled randomized clinical trials will have been performed that clinical practice can be evidence-based, rather than anecdote-based. Given the significant emotional, physical and healthcare costs associated with CPP, there is a vital need for these trials to be performed.

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