4.6 Article

Association of endocannabinoids with pain in endometriosis

Journal

PAIN
Volume 163, Issue 1, Pages 193-203

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/j.pain.0000000000002333

Keywords

Endometriosis; Dysmenorrhea; Abdominal pain; Dyspareunia; Endocannabinoids; Prostaglandins; 2-AG; Peritoneal fluid; Serum

Funding

  1. University of Bern
  2. Department of Gynecology and Gynecological Oncology at Inselspital of Bern
  3. NCCR-TransCure

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This case-control study found that levels of endocannabinoids (eCBs) are significantly influenced by both noncyclic and cyclic abdominal pain, suggesting a potential role of the eCB system in endometriosis-associated pain.
Endocannabinoid (eCB) levels fluctuate in inflammatory conditions and as such may take part in endometriosis-associated pain or even in endometriosis pathogenesis. In this case-control (23 cases and 19 controls) study, targeted lipids were measured in the serum and peritoneal fluid collected during laparoscopy. Endometriosis was confirmed histologically. Dysmenorrhea, abdominal pain, and dyspareunia were assessed using the Numeric Rating Scale for pain. Steroids, eCBs, and related lipids were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Tumor necrosis factor alpha, IL-8, PAPP-A, PP14, RANTES, OPG, MIDKINE, MCP-1, VEGF, leptin, and defensins were quantified by ELISA. We found that eCB levels were significantly influenced by both noncyclic and cyclic abdominal pain. Specifically, women suffering from noncyclic abdominal pain were characterized by a higher 2-AG level in the peritoneal fluid throughout the menstrual cycle, whereas women suffering from dysmenorrhea had higher 2-AG levels and lower AEA levels during the proliferative phase alone. In addition, 2-AG positively correlated with prostaglandin E2 (PGE2), and the ratio AEA/2-AG positively correlated with defensins, suggesting a possible link between endocannabinoids system and inflammatory pain. The results of the current study indicate that the eCB system may play a role in endometriosis-associated pain, but additional studies are needed to investigate the causal relationship.

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