Oxidation-sensitive nociception involved in endometriosis-associated pain
Kristeena Ray1, Johannes Fahrmann, Brenda Mitchell
1Departments of Pharmacology, Physiology, and Toxicology Biochemistry and Microbiology, and Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA, USA Department of Basic Sciences, University of North Dakota, Grand Forks, ND, USA.
Oxidatively modified lipoproteins in peritoneal fluid contribute to endometriosis pain. Antioxidants and anti-inflammatory drugs can suppress this pain, offering new treatment avenues for chronic pain conditions.
Area of Science:
- Biomedical research
- Pain mechanisms
- Gynecological disorders
Background:
- Endometriosis is linked to chronic pelvic pain, with peritoneal fluid containing inflammatory markers and pain mediators.
- Oxidatively modified lipoproteins are abundant in the peritoneal fluid of women with endometriosis.
- Endometriotic tissue is innervated with nociceptors, suggesting a role for pain signaling molecules.
Purpose of the Study:
- To investigate if oxidatively modified lipoproteins in peritoneal fluid are a source of nociceptive molecules driving endometriosis-associated pain.
- To determine the ability of these molecules to induce nociception and if antioxidants can suppress it.
- To explore the impact of these molecules on gene expression in endometrial cells.
Main Methods:
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect lipoprotein-derived oxidation-sensitive pain molecules.
- Animal models (mice and rats) to assess hypothermia and nociception induced by oxidatively modified lipoproteins.
- In vitro studies on human endometrial cells treated with oxidatively modified lipoproteins or peritoneal fluid.
Main Results:
- Oxidized lipoproteins generated eicosanoids similar to those found in peritoneal fluid.
- Oxidatively modified lipoproteins induced hypothermia and nociception in animal models.
- Antioxidants (vitamin E, N-acetylcysteine) and indomethacin suppressed the pain-inducing effects of oxidized lipoproteins.
- Treatment with oxidized lipoproteins or peritoneal fluid upregulated genes in opioid and inflammatory pathways in endometrial cells.
Conclusions:
- Oxidatively modified lipoproteins in peritoneal fluid are a significant source of nociceptive molecules contributing to endometriosis-associated pain.
- Antioxidant and anti-inflammatory interventions show potential in mitigating this pain.
- These findings have implications for treating chronic pain in endometriosis and other related conditions.
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