Oxidation-sensitive nociception involved in XXXX .

@entity1 @entity19 @entity2371 @entity46 @entity158 @entity1118 @entity2332
UNASSIGNED: Endometriosis is a disease characterized by the growth of endometrial tissue outside the uterus and is associated with chronic @entity2371 . Peritoneal fluid (PF) of @entity1 with @entity46 is a dynamic milieu and is rich in inflammatory markers, @entity158 -inducing prostaglandins prostaglandin E2 and prostaglandin F2a, 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 @entity1 with @entity46 and the ability of antioxidant supplementation to alleviate @entity158 . We hypothesized that oxidatively modified lipoproteins present in the PF are the major source of nociceptive molecules that play a key role in @entity158 . In this study, PF obtained from @entity1 with @entity46 or control @entity1 were used for (1) the detection of lipoprotein-derived oxidation-sensitive @entity158 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 @entity2332 (intracerebroventricular) in CD-1 @entity19 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 @entity158 -inducing ability of oxidatively modified lipoproteins. Treatment of @entity1 endometrial cells with oxidatively modified lipoproteins or PF from @entity1 with @entity46 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 @entity158 but also on other diseases associated with @entity1118 .
