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. 2022 Jan 1;163(1):193-203.
doi: 10.1097/j.pain.0000000000002333.

Association of endocannabinoids with pain in endometriosis

Thomas Andrieu  1 , Andrea Chicca  2 , Daniele Pellegata  2 , Nick A Bersinger  1 , Sara Imboden  1   3 , Konstantinos Nirgianakis  1   3 , Juerg Gertsch  2 , Michael D Mueller  1   3
Affiliations

Association of endocannabinoids with pain in endometriosis

Thomas Andrieu et al. Pain. .

Abstract

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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Conflict of interest statement

A. Chicca and J. Gertsch are cofounders of Synendos Therapeutics, a spin-off company of the University of Bern that develops first-in-class eCB modulators. The remaining authors have no conflicts of interest to declare.

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

Figure 1.
Figure 1.
Targeted lipidomics in PF. Descriptive plots for 2-AG (A), OEA (B), and PGE2 (C) in the proliferative (“1 = Pro”) and secretory (“2 = Se”) phases. Descriptive plots for C18-20:4 PC (D) in patients without (“0”) and with endometriosis (“1”). Descriptive plots for 2-AG (E) and AA (F) in patients with low (“0”) and high (“1”) abdominal pain. Descriptive plots for 2-AG (G) and AEA/2-AG (H) across the menstrual cycle in patients with low (white circles) and high (dark circles) dysmenorrhea. Descriptive plot for AEA (I) in patients with low (“0”) and high (“1”) dyspareunia. The number of patients is indicated on the figure. The values represent mean ± SEM. ANOVA, *P < 0.05, **P < 0.01 (A–F, I). Two-way ANOVA, Tukey post hoc test, *P < 0.05 (G and H). ANOVA, analysis of variance.
Figure 2.
Figure 2.
Targeted lipidomics in the serum. Descriptive plots for AA (A) in the proliferative (“1 = Pro”) and secretory (“2 = Se”) phases. Descriptive plots for LEA (B) and OEA (C) in patients without (“0”) and with endometriosis (“1”). Descriptive plots for AA (D) across the menstrual cycle in patients with low (white circles) and high (dark circles) dysmenorrhea. The number of patients is indicated on the figure. The values represent mean ± SEM. ANOVA, *P < 0.05, **P < 0.01 (A–C). Two-way ANOVA, Tukey post hoc test, *P < 0.05 (D). ANOVA, analysis of variance.
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