Association of endocannabinoids with pain in endometriosis

Andrieu, Thomas; Chicca, Andrea; Pellegata, Daniele; Bersinger, Nick A.; Imboden, Sara; Nirgianakis, Konstantinos; Gertsch, Jürg; Mueller, Christoph

doi:10.1097/j.pain.0000000000002333

Cited by 10 publications

(3 citation statements)

References 45 publications

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“…Studies employing lipidomics have highlighted dysregulated lipid metabolism in endometriosis, including changes in phospholipids, glycerolipids, sphingolipids, and sterols [35][36][37][38][39][40]. Furthermore, lipidomics investigations have unveiled the role of bioactive lipids, such as prostaglandins, and leukotrienes, in modulating inflammatory responses and pain perception in endometriosis [39,41]. Targeting specific lipid pathways through pharmacological interventions or dietary modifications may offer novel therapeutic strategies for managing endometriosis-related symptoms and improving patient outcomes [5].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Value of Menstrual Blood Lipidomics in Endometriosis: A Pilot Study

Starodubtseva,

Chagovets,

Tokareva

et al. 2024

Preprint

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Endometriosis is a prevalent chronic inflammatory disease characterized by a considerable delay between initial symptoms and diagnosis through surgery. The pressing need for a timely, non-invasive diagnostic solution underscores the focus of current research efforts. This study examines the diagnostic potential of the menstrual blood lipidome. The lipid profile of 39 samples (23 women with endometriosis and 16 patient of control group) was acquired using reverse-phase high-performance liquid chromatography-mass spectrometry with LipidMatch processing and identification. Profiles were normalized based on total ion counts. Significant differences in lipids were determined using the Mann-Whitney test. Lipids for the diagnostic model, based on logistic regression, were selected using a combination of variance importance projection filters and Akaike information criteria. Levels of ceramides, sphingomyelins, cardiolipins, triacylglycerols, acyl- and alkenyl-phosphatidylethanolamines, and alkenyl-phosphatidylcholines increased, while acyl- and alkyl-phosphatidylcholines decreased in cases of endometriosis. PE P-16:0/18:1 and CL 16:0_18:0_22:5_22:6 serve as marker lipids in the diagnostic model, exhibiting a sensitivity of 81% and specificity of 85%. The diagnostic approach based on dried spots of menstrual blood holds promise as an alternative to traditional non-invasive methods for endometriosis screening.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Value of Menstrual Blood Lipidomics in Endometriosis: A Pilot Study

Starodubtseva,

Chagovets,

Tokareva

et al. 2024

Preprint

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“…One such study showed that the levels of 2-AG and AEA were significantly higher in the peritoneal fluid of EMS patients as compared to individuals without EMS, which was also correlated to higher abdominal pain experienced by patients. Although the authors suggest that the ECs identified in their study are involved in deepening the abdominal inflammatory pain, low sample size and unaccounted comorbidities should be considered when correlating ECS involvement in driving the inflammatory pain in the peritoneum (Andrieu et al 2022). Nevertheless, these findings demonstrate a complex and at times contradictory role of the ECS in pain modulation and management.…”

Section: The Endocannabinoid System and Painmentioning

confidence: 96%

Role of the endocannabinoid system in the pathophysiology of endometriosis and therapeutic implications

et al. 2022

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Endometriosis patients experience debilitating chronic pain, and the first-line treatment is ineffective at managing symptoms. Although surgical removal of the lesions provides temporary relief, more than 50% of the patients experience disease recurrence. Despite being a leading cause of hysterectomy, endometriosis lacks satisfactory treatments and a cure. Another challenge is the poor understanding of disease pathophysiology which adds to the delays in diagnosis and overall compromised quality of life. Endometriosis patients are in dire need of an effective therapeutic strategy that is both economical and effective in managing symptoms, while fertility is unaffected. Endocannabinoids and phytocannabinoids possess anti-inflammatory, anti-nociceptive, and anti-proliferative properties that may prove beneficial for endometriosis management, given that inflammation, vascularization, and pain are hallmark features of endometriosis. Endocannabinoids are a complex network of molecules that play a central role in physiological processes including homeostasis and tissue repair, but endocannabinoids have also been associated in the pathophysiology of several chronic inflammatory diseases including endometriosis and cancers. The lack of satisfactory treatment options combined with the recent legalization of recreational cannabinoids in some parts of the world has led to a rise in self-management strategies including the use of cannabinoids for endometriosis-related pain and other symptoms. In this review, we provide a comprehensive overview of endocannabinoids with a focus on their potential roles in the pathophysiology of endometriosis. We further provide evidence-driven perspectives on the current state of knowledge on endometriosis-associated pain, inflammation, and therapeutic avenues exploiting the endocannabinoid system for its management.

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“…This in turn leads to people experiencing hyperalgesia, which has been correlated with altered expression of TRPV1 in the peritoneum of people with endometriosis [76]. Levels of 2-AG and AEA have also been observed to be significantly higher in the peritoneal fluid of people with endometriosis, and this was associated with relatively higher abdominal pain [77]. The protective role of the ECS was observed in people with endometriosis, where immunohistochemistry revealed that cannabinoid agonists inhibit endometrial cell proliferation [65].…”

Section: Potential Interplay Of the Ecs And Endometriosismentioning

confidence: 99%

Cannabis and Endometriosis: The Roles of the Gut Microbiota and the Endocannabinoid System

Farooqi,

Bhuyan,

Low

et al. 2023

JCM

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Endometriosis, a chronic condition affecting around 10–14% of women, is challenging to manage, due to its complex pathogenesis and limited treatment options. Research has suggested a potential role of the gut microbiota and the endocannabinoid system in the development and progression of endometriosis. This narrative review aims to explore the role of, and any potential interactions between, the endocannabinoid system (ECS) and the gut microbiota in endometriosis. This review found that both the ECS and microbiota influence endometriosis, with the former regulating inflammation and pain perception and the latter influencing immune responses and hormonal balance. There is evidence that a dysregulation of the endocannabinoid system and the gut microbiota influence endometriosis symptoms and progression via changes in CB1 receptor expression and increased circulating levels of endocannabinoids. Microbial imbalances in the gut, such as increases in Prevotella, have been directly correlated to increased bloating, a common endometriosis symptom, while increases in E. coli have supported the bacterial contamination hypothesis as a potential pathway for endometriosis pathogenesis. These microbial imbalances have been correlated with increases in inflammatory markers such as TNF-α and IL-6, both often raised in those with endometriosis. Protective effects of the ECS on the gut were observed by increases in endocannabinoids, including 2-AG, resulting in decreased inflammation and improved gut permeability. Given these findings, both the ECS and the gut microbiota may be targets for therapeutic interventions for endometriosis; however, clinical studies are required to determine effectiveness.

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Association of endocannabinoids with pain in endometriosis

Abstract: Supplemental Digital Content is Available in the Text. Targeted lipids and inflammation modulators were analyzed in abdominal fluid and serum revealing an association between endocannabinoids (2-AG and AEA) and gynecological pain.

Cited by 10 publications

References 45 publications

Diagnostic Value of Menstrual Blood Lipidomics in Endometriosis: A Pilot Study

Diagnostic Value of Menstrual Blood Lipidomics in Endometriosis: A Pilot Study

Role of the endocannabinoid system in the pathophysiology of endometriosis and therapeutic implications

Cannabis and Endometriosis: The Roles of the Gut Microbiota and the Endocannabinoid System

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