Beyond the Lesions: Unraveling the Multifactorial Nature of Endometriosis and Chronic Overlapping Pain

In: Archives of Women Health and Care · 2024 · vol. 7(4) · doi:10.31038/awhc.2024741 · W4401924798
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This commentary discusses how endometriosis, beyond its physical lesions, is a multifactorial disease involving central nervous system changes and often co-occurring with other chronic overlapping pain conditions.

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This commentary discusses endometriosis as an estrogen-dependent neuroinflammatory condition characterized by endometrial-like lesions and varied pain symptoms, noting that diagnosis may take 10 years or more and that conventional lesion-focused treatments often yield suboptimal outcomes with limited correlation between lesion extent and pain severity. It reviews evidence that central nervous system–mediated mechanisms, including altered sensory processing and brain changes, may contribute to pain, and frames endometriosis as frequently heterogeneous and comorbid with chronic overlapping pain conditions (COPCs) that share central pain-processing mechanisms. The authors summarize their recently conducted cross-sectional survey of 525 women with chronic pelvic-abdominal pain, where 25% reported endometriosis, finding higher COPC prevalence and worse pain outcomes in those with endometriosis as well as worse outcomes associated with a greater number of pain diagnoses, while acknowledging the complexity of multimorbidity assessment and care. This paper is centrally about endometriosis — it argues for moving beyond lesion-based explanations toward a multifactorial, centrally mediated model that incorporates COPCs.

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Archives of Women Health and Care Volume 7 Issue 4Research Open ARCH Women Health Care, Volume 7(4): 1–2, 2024 Short Commentary Beyond the Lesions: Unraveling the Multifactorial Nature of Endometriosis and Chronic Overlapping Pain Emily J. Bartley, PhD*1, Meryl J. Alappattu, PhD, DPT2 and Georgine Lamvu, MD, MPH3,4 1University of Florida, College of Dentistry, Pain Research & Intervention Center of Excellence 2University of Florida, College of Public Health and Health Professions, Pain Research & Intervention Center of Excellence 3University of Central Florida, College of Medicine 4Orlando VA Healthcare System, Division of Surgery, Gynecology Section *Corresponding author: Emily J. Bartley, Ph.D. Assistant Professor, Pain Research & Intervention Center of Excellence, Department of Community Dentistry & Behavioral Science, University of Florida,1329 SW 16th St, Suite 5192, Gainesville, FL 32610, Office: 352-273-8934 Received: August 17, 2024; Accepted: August 20, 2024; Published: August 27, 2024 Commentary Endometriosis has a long and complex history in the field of medicine, with its etiology and treatment being sources of debate for many years. This estrogen-dependent neuro inflammatory disease is marked by the presence of endometrial-like tissue outside the uterus, affecting approximately 10% of women of reproductive age. The disease’s symptoms are varied, with pain being a defining characteristic, including dysmenorrhea, painful intercourse, chronic pelvic pain, and bowel and bladder pain. These symptoms can be profoundly debilitating, adversely impacting quality of life and psychological health [1]. Compounding these challenges is the staggering reality that diagnosis can take 10 years or more, prolonging the suffering of those affected and underscoring the urgent need for greater awareness and more efficient diagnostic methods for the disease. Adding to its existing burden, endometriosis remains incurable, with treatments based on the suspected etiology of the pelvic pain and primarily focused on symptom relief. While such treatments can benefit those whose pain is driven by peripheral mechanisms, therapies that primarily target the periphery are often only effective for individuals experiencing anatomically localized pain. In fact, nearly 50% of medical and surgical treatments are unsuccessful, leaving patients with ongoing pain even after the suppression or surgical removal of endometriosis lesions. Moreover, there is little correlation between the extent of the disease and the severity of pain experienced, suggesting that factors beyond the lesions themselves may play a significant role in the pain associated with endometriosis. Over the past two decades, a growing body of evidence has supported this notion, indicating that endometriosis is not merely a disease defined by the presence of endometrial lesions but one that is also mediated by central nervous system factors, including altered sensory processing as well as structural and functional changes in the brain [2-7]. In recent years, endometriosis has increasingly been recognized as a heterogeneous condition that often coexists with other organic pain disorders. Collectively referred to as chronic overlapping pain conditions (COPCs), these disorders frequently occur together and include endometriosis, vulvodynia, irritable bowel syndrome, temporomandibular disorder, chronic fatigue syndrome, interstitial cystitis/painful bladder syndrome, fibromyalgia, tension-type and migraine headaches, and chronic low back pain. COPCs predominantly affect females and exhibit a high degree of co-prevalence. Although the underlying causes of these conditions remain poorly understood, they are generally believed to share common pathophysiological mechanisms, with alterations in central nervous system processing likely contributing to the pain experienced. Substantial evidence suggests that a higher prevalence of these conditions is associated with more frequent and prolonged pelvic pain episodes, increased pain severity, impairments in daily activities, reduced treatment efficacy, and declines in psychological functioning and quality of life [8-10]. It is estimated that over 95% of patients with endometriosis report having at least one overlapping pain condition. Unfortunately, these comorbidities are often resistant to singular treatments and may even exacerbate pelvic pain severity and reduce therapeutic effectiveness. Despite this understanding, endometriosis has traditionally been classified and treated as a peripheral disease, focusing on the removal or suppression of endometrial lesions—an approach that has yielded suboptimal outcomes [11]. Why do these treatments often fall short? Given the heterogeneity of endometriosis and its common overlap with other pain conditions, one possibility is that our treatment efforts are not appropriately targeted, failing to address centrally mediated factors that impact endometriosis pain, including the multimorbidity of the disease. Recognizing this gap, our team recently conducted a study examining the prevalence of COPCs in a sample of 525 women with chronic pelvic-abdominal pain (CPP), 25% of whom also reported endometriosis. Not surprisingly, compared to women with just CPP , those with endometriosis reported more adverse pain outcomes including greater pelvic pain severity and interference, as well as a higher degree of burden associated with their pelvic pain. They also reported a higher prevalence of COPCs, including fibromyalgia, chronic fatigue syndrome, and temporomandibular disorder. Even ARCH Women Health Care, Volume 7(4): 2–2, 2024 Emily J. Bartley (2024) Beyond the Lesions: Unraveling the Multifactorial Nature of Endometriosis and Chronic Overlapping Pain more striking, approximately 25% of women with endometriosis reported three or more COPCs, compared to only 12% of women with just CPP . Interestingly, a higher prevalence of COPCs was linked to more adverse pain outcomes, regardless of an endometriosis diagnosis. These findings align with previous data showing that as the number of pain diagnoses increases, symptoms become significantly more severe. More importantly, our results underscore the substantial burden that multimorbidity places on patient functioning [12,13]. Given the impact of co-occurring pain, screening and treatment of COPCs in endometriosis could be crucial steps toward improving clinical care. However, achieving effective treatments for these comorbidities is often complex, as providers frequently encounter challenges stemming from limited resources and inadequate education about endometriosis and chronic pelvic pain, making it difficult to systematically assess and manage multiple pain conditions. Additionally, patients with endometriosis often endure long, fragmented care across multiple medical specialties, with many providers lacking extensive training in pain management and focusing on treatment from their own medical lens. Unfortunately, this approach often overlooks the multidimensional nature of the disease, potentially neglecting the central mechanisms driving endometriosis pain [14]. Patients with comorbidities often face an array of challenges that can significantly hinder treatment. To make meaningful strides in disease management, it is crucial that we prioritize endometriosis care and expand the focus of treatment beyond the lesions. The presence of COPCs should be a key consideration in patient management, as those with multiple pain comorbidities likely require a broader and more comprehensive spectrum of therapeutic targets to effectively manage their symptoms. Alongside pharmacological management, this could include supportive counseling or psychotherapy to address maladaptive beliefs and emotional distress that often accompany pain, integrative and complementary therapies (e.g., yoga, mindfulness), self-management strategies (e.g., physical activity, stress management), and physical therapy to treat myofascial pain and dysfunction. Given the decades of research demonstrating that endometriosis is not merely a disease of lesions, it is time we consider other contributing biological, psychological, and social factors that affect patient functioning and well-being. We desperately need a paradigm shift in both the management of endometriosis and the way patients are informed about the disease and their treatment options. This transformation could enhance patient care and provide a more holistic approach to pain management. Not only could this offer a vital opportunity to alleviate the profound burden of endometriosis, but it may also dramatically improve the overall quality of life for those affected. Funding Research reported in this publication was supported by the National Institutes of Health (1R21HD104957). References 1. Shafrir AL, Farland LV , Shah DK, Harris HR, et al. (2018) Risk for and consequences of endometriosis: A critical epidemiologic review. Best Practice & Research Clinical Obstetrics & Gynaecology 51: 1-15. [crossref] 2. Vercellini P , Crosignani PG, Abbiati A, Somigliana E, et al. (2009) The effect of surgery for symptomatic endometriosis: The other side of the story. Hum Reprod Update 15(2). [crossref] 3. Guo SW (2009) Recurrence of endometriosis and its control. Hum Reprod Update 15(4). [crossref] 4. Vercellini P , Fedele L, Aimi G, Pietropaolo G, et al. (2006) Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: A multivariate analysis of over 1000 patients. Human Reproduction 22(1). [crossref] 5. As-Sanie S, Kim J, Schmidt-Wilcke T, Sundgren PC, et al. (2016) Functional connectivity is associated with altered brain chemistry in women with endometriosis- associated chronic pelvic pain. J Pain 17(1). [crossref] 6. As-Sanie S, Harris RE, Harte SE, Tu FF , et al. (2013) Increased pressure pain sensitivity in women with chronic pelvic pain. Obstetrics and Gynecology 122(5). [crossref] 7. Bajaj P , Bajaj P , Madsen H, Arendt-Nielsen L (2003) Endometriosis is associated with central sensitization: A psychophysical controlled study. J Pain 4(7). [crossref] 8. Maixner W , Fillingim RB, Williams DA, Smith SB, Slade GD (2016) Overlapping chronic pain conditions: Implications for diagnosis and classification. J Pain 17(supp9). [crossref] 9. Till SR, Nakamura R, Schrepf A, As-Sanie S (2022) Approach to diagnosis and management of chronic pelvic pain in women: Incorporating chronic overlapping pain conditions in assessment and management. Obstet Gynecol Clin North Am 49(2). [crossref] 10. Leuenberger J, Kohl Schwartz AS, Geraedts K, Haeberlin F , et al. (2022) Living with endometriosis: Comorbid pain disorders, characteristics of pain and relevance for daily life. Eur J Pain 26(5). [crossref] 11. Hernández Cardona MI, Ajewole C, Lewis H, Carrillo JF , et al. (2023) Time to move beyond surgical classification systems for endometriosis. Int J Gynaecol Obstet 163(1). [crossref] 12. Bartley EJ, Alappattu MJ, Manko K, Lewis H, et al. (2024) Presence of endometriosis and chronic overlapping pain conditions negatively impacts the pain experience in women with chronic pelvic-abdominal pain: A cross-sectional survey. Womens Health V(20). [crossref] 13. Ohrbach R, Sharma S, Fillingim RB, Greenspan JD, et al. (2020) Clinical characteristics of pain among five chronic overlapping pain conditions. J Oral Facial Pain Headache 34(s29-s42). [crossref] 14. Greene R, Stratton P , Cleary SD, Ballweg ML, Sinaii N (2009) Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis. Fertility and Sterility 91(1). [crossref] Citation: Bartley EJ (2024) Beyond the Lesions: Unraveling the Multifactorial Nature of Endometriosis and Chronic Overlapping Pain. ARCH Women Health Care Volume 7(4): 1-2.

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