Oxidation-sensitive nociception involved in endometriosis-associated pain

Autor: Kristeena Ray, Johannes F. Fahrmann, Carla Cook, Dennis Paul, Stephen A. Brose, Svetlana A. Golovko, Mikhail Y. Golovko, Nalini Santanam, Courtney Crain, Holly King, Brenda L Mitchell
Rok vydání: 2015
Předmět:
Nociception
Time Factors
Indomethacin
Lipoxygenase
Endometriosis
Dinoprost
Antioxidants
Body Temperature
Rats
Sprague-Dawley
Mice
chemistry.chemical_compound
Tandem Mass Spectrometry
Ascitic Fluid
Vitamin E
Prostaglandin E2
Pain Measurement
Anti-Inflammatory Agents
Non-Steroidal
Chronic pain
Middle Aged
Peroxides
Lipoproteins
LDL
Neurology
Anesthesia
Nociceptor
Female
lipids (amino acids
peptides
and proteins)
medicine.symptom
medicine.drug
Adult
medicine.medical_specialty
Adolescent
Prostaglandin
Inflammation
Pelvic Pain
Thiobarbituric Acid Reactive Substances
Article
Dinoprostone
Young Adult
Internal medicine
medicine
Animals
Humans
Analysis of Variance
business.industry
Pelvic pain
medicine.disease
Rats
Anesthesiology and Pain Medicine
Endocrinology
chemistry
Prostaglandin-Endoperoxide Synthases
Neurology (clinical)
business
Zdroj: Pain. 156:528-539
ISSN: 0304-3959
DOI: 10.1097/01.j.pain.0000460321.72396.88
Popis: Endometriosis is a disease characterized by the growth of endometrial tissue outside the uterus and is associated with chronic pelvic pain. Peritoneal fluid (PF) of women with endometriosis is a dynamic milieu and is rich in inflammatory markers, pain-inducing prostaglandins prostaglandin E2 and prostaglandin F2α, and lipid peroxides; and the endometriotic tissue is innervated with nociceptors. Our clinical study showed that the abundance of oxidatively modified lipoproteins in the PF of women with endometriosis and the ability of antioxidant supplementation to alleviate endometriosis-associated pain. We hypothesized that oxidatively modified lipoproteins present in the PF are the major source of nociceptive molecules that play a key role in endometriosis-associated pain. In this study, PF obtained from women with endometriosis or control women were used for (1) the detection of lipoprotein-derived oxidation-sensitive pain molecules, (2) the ability of such molecules to induce nociception, and (3) the ability of antioxidants to suppress this nociception. LC-MS/MS showed the generation of eicosanoids by oxidized-lipoproteins to be similar to that seen in the PF. Oxidatively modified lipoproteins induced hypothermia (intracerebroventricular) in CD-1 mice and nociception in the Hargreaves paw withdrawal latency assay in Sprague-Dawley rats. Antioxidants, vitamin E and N-acetylcysteine, and the nonsteroidal anti-inflammatory drug indomethacin suppressed the pain-inducing ability of oxidatively modified lipoproteins. Treatment of human endometrial cells with oxidatively modified lipoproteins or PF from women with endometriosis showed upregulation of similar genes belonging to opioid and inflammatory pathways. Our finding that oxidatively modified lipoproteins can induce nociception has a broader impact not only on the treatment of endometriosis-associated pain but also on other diseases associated with chronic pain.
Databáze: OpenAIRE
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