dinoprost and Pelvic-Pain

Painful menstruation is a cyclic painful condition that adversely affects the woman's wellbeing for a large part of her life. Its pathogenesis is not always understood. Prostaglandins seem to be intimately involved in primary dysmenorrhoea although it is difficult to understand the underlying cause for their excessive secretion. Abnormalities in plasma steroid levels could account for the disturbance, especially significantly elevated plasma levels of estradiol in the luteal phase. Plasma levels of vasopressin appear to be higher in women with dysmenorrhea suggesting a possible aetiological role in the uterine prostaglandin synthesis. The main aim of diagnosis is to distinguish those cases with secondary dysmenorrhoea due to endometriosis and chronic pelvic inflammatory disease and treat them accordingly although the exact role of endometriosis remains unclear. The development of sonographic and magnetic resonance imaging techniques (MRI) allow pre-operative diagnosis of adenomyosis, a difficult to diagnose cause of dysmenorrhea and pelvic pain. Medication is usually required for all cases of moderate to severe painful menstruation. Apart from pharmacological agents, several techniques have been used including relaxation therapy, hypnosis, manipulation, psychotherapy, acupuncture, biofeedback techniques, surgery e.g. Despite the high prevalence of painful menstruation, its frequency and severity is very often underestimated.

Topics: Adolescent; Amenorrhea; Contraceptives, Oral, Hormonal; Dinoprost; Dysmenorrhea; Female; Humans; Pelvic Pain; Prostaglandin Antagonists; Sympathomimetics

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.

Topics: Adolescent; Adult; Analysis of Variance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Ascitic Fluid; Body Temperature; Dinoprost; Dinoprostone; Endometriosis; Female; Humans; Indomethacin; Lipoproteins, LDL; Lipoxygenase; Mice; Middle Aged; Nociception; Pain Measurement; Pelvic Pain; Peroxides; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Thiobarbituric Acid Reactive Substances; Time Factors; Vitamin E; Young Adult

Is the occurrence of pelvic pain in women with ovarian endometrioma associated with coexisting peritoneal lesions (PLs)?. Pelvic pain in women with ovarian endometrioma is usually associated with coexisting PLs. An increased tissue inflammatory reaction with elevated prostaglandin (PG) production may be responsible for the generation of pain.. Severe pelvic pain in women with ovarian endometrioma is reported to be associated with deeply infiltrating endometriosis. However, information on pelvic pain in women with ovarian endometriosis with and without coexistent peritoneal superficial lesions is limited.. Retrospective clinical study with case-controlled biological research using prospectively collected tissue samples derived from women with and without endometriosis and their retrospective evaluation.. We performed a retrospective cohort study conducted in 2988 cases who had laparoscopic surgery for indications of ectopic pregnancy, tubal infertility and other benign gynecologic diseases. We analyzed the occurrence of pelvic pain in the cases with ovarian endometrioma according to the distribution of coexisting PLs and pattern of intrapelvic adhesions. Inflammatory reaction of eutopic and ectopic endometria was measured by immunoreaction to macrophage marker, CD68. The tissue expression of cyclooxygenase (COX) 2 was examined by immunohistochemistry and tissue concentrations of PG F2α were measured by ELISA.. Among the 2988 surgical cases, 350 (11.7%) were found to have ovarian endometrioma at laparoscopy. Coexisting PLs were present in 269 of these women and in this group 85.4% of cases experienced pelvic pain and 14.6% had no pain. In contrast, among the 81 women with ovarian endometrioma only, 38.3% cases experienced pelvic pain and 61.7% cases had no pain and the difference between the groups was statistically significant (P < 0.01). The infiltration of CD68-immunoreactive macrophages was significantly higher in the eutopic and ectopic endometria of women with peritoneal endometriosis than in ovarian endometrioma. The tissue expression of COX2 and levels of PGF2α were significantly higher in both the eutopic and ectopic endometria derived from women with peritoneal endometriosis than in similar tissues derived from women with ovarian endometrioma.. Lack of evaluation in the detection of general or disseminated deeply infiltrating endometriosis in the pelvic cavity could be a bias or limitation in this study. Further multicenter prospective studies are needed to strengthen our current findings.. Our findings may provide some new insights to understand the physiopathology of pelvic pain in women with ovarian cystic endometriosis and may hint at proper surgical manipulation to prevent the recurrence of pelvic pain in these women.. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology of Japan. There is no conflict of interest related to this study.. Not applicable.

Topics: Adult; Case-Control Studies; Cohort Studies; Cyclooxygenase 2; Dinoprost; Endometriosis; Female; Humans; Incidence; Japan; Laparoscopy; Macrophages; Middle Aged; Ovarian Diseases; Pelvic Pain; Peritoneal Diseases; Prospective Studies; Retrospective Studies; Tissue Adhesions; Young Adult

To investigate the activity of different forms of endometriosis implants by clinical and biochemical evaluation.. Prospective, blinded study.. Tertiary-care university hospital.. Forty-seven infertile patients with minimal or mild endometriosis diagnosed at laparoscopy were included in the clinical investigation.. Patients were submitted to a preoperative evaluation of endometriosis-associated dysmenorrhea by means of a 10-point linear analog scale and to laparoscopic staging of endometriosis following a current classification system. In the biochemical investigation, tissue samples from different endometriosis lesions and control tissues were assessed for prostaglandin (PG) F(2 alpha) production.. Evaluation of the correlation between endometriosis-associated dysmenorrhea and the extent of the disease. Evaluation of the production of PGF(2 alpha) by the different tissues sampled.. No positive correlation was present between any of the implant subgroups and the associated dysmenorrhea. White peritoneal implants were associated with milder pain symptoms than black or red lesions. The biologic activity of red and black superficial implants, expressed as the production of PGF(2 alpha), was similar.. No positive correlation was demonstrated between endometriosis-associated dysmenorrhea and the current classification of endometriosis, which includes characterization of the different morphologic aspects of superficial endometriosis implants.

Topics: Adult; Dinoprost; Dysmenorrhea; Endometriosis; Female; Humans; Laparoscopy; Pelvic Pain; Preoperative Care; Prospective Studies