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An in vivo mouse model of primary dysmenorrhea.

ABSTRACT: Primary dysmenorrhea (PD) is a common gynecological disorder. Hitherto, animal models which recapitulate clinical features of PD have not been fully established. We aimed to examine whether a pain model in mice could mimic the clinic features of PD. After pretreated with estradiol benzoate (1 mg/kg/day) intraperitoneally (i.p.) for 3 consecutive days, non-pregnant female Imprinting Control Region mice (6-8 weeks old) was injected with 0.4 U of oxytocin to induce the stretching or writhing response which was recorded for a time period of 30 min. During the writhing period, the uterine artery blood flow alterations were examined by Doppler ultrasound detection. After writhing test, the uterine morphological changes were observed by hematoxylin and eosin (H&E) staining histopathology. In addition, enzyme-linked immunosorbent assay kit was used to measure the levels of prostaglandins F2?/prostaglandins E2 (PGF2?/PGE2) and TXB2 (a metabolite of TXA2)/6-keto-PGF1? (a metabolite of PGI2) in the uterine tissue homogenates and plasma, respectively. Western blot analyses were performed to determine the expressions of oxytocin receptor (OTR), beta2-adrenergic receptor (beta2-AR), and cyclooxygenase-2 (COX-2) in uterine, which are responsible for the uterine contraction. The writhing response only occurred in the estrogen pretreated female mice. The area of uterine myometrium significantly decreased along with the increased thickness in the oxytocin-induced estrogen pretreated mice model. The uterine artery blood flow velocity dropped, while the pulsatility index and resistance index slightly increased after the injection of oxytocin. The PGF2?/PGE2 level significantly increased and the plasma TXB2/6-keto-PGF1? level significantly enhanced. Compared with the control group, the uterine histopathology demonstrated moderate to severe edema of endometrium lamina propria. In consistent with the uterine morphological changes, a significant reduction of beta2-AR and a significant increase of OTR and COX-2 in the uterine tissue were observed. The writhing response was caused by the abnormal contraction of uterus. The uterine spasm and ischemia changes of oxytocin-induced estrogen pretreated female mice model were similar to the pathology of human PD. We reported an in vivo mice model, which can be used to study PD and for clinical therapeutic evaluations.

SUBMITTER: Yang L

PROVIDER: S-EPMC4548002 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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An in vivo mouse model of primary dysmenorrhea.

Yang Lu L Cao Zhengyu Z Yu Boyang B Chai Chengzhi C

Experimental animals 20150424 3

Primary dysmenorrhea (PD) is a common gynecological disorder. Hitherto, animal models which recapitulate clinical features of PD have not been fully established. We aimed to examine whether a pain model in mice could mimic the clinic features of PD. After pretreated with estradiol benzoate (1 mg/kg/day) intraperitoneally (i.p.) for 3 consecutive days, non-pregnant female Imprinting Control Region mice (6-8 weeks old) was injected with 0.4 U of oxytocin to induce the stretching or writhing respon ...[more]

PMID: 25912320

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Project description:Primary dysmenorrhea is a common gynecological disease with typical clinical symptoms and diverse treatment methods. Acupoint patch therapy is one of the traditional external treatments of traditional Chinese medicine, with a long history, and has been widely used in the treatment of many diseases in China. Graphene nuangong acupoint plaster (GNGAP) developed based on traditional acupoints and new materials have been used in the clinical treatment of primary dysmenorrhea, and satisfactory therapeutic effects have been achieved. However, the underlying mechanisms of GNGAP still need further investigation. In this study, we used estradiol benzoate combined with oxytocin intraperitoneally to establish dysmenorrhea model rats, and observed the torsion response, uterine organ coefficients, prostaglandin levels and metabolite changes of rats with dysmenorrhea model after the intervention of GNGAP, to elucidate the mechanism of the effect of GNGAP. Compared with normal rats, the dysmenorrhea model rats exhibited increased writhing response and latency time, increased uterine organ coefficient, and significant changes in 79 metabolites. Twenty-three significantly enriched pathways were discovered, including amino acid metabolism, arachidonic acid metabolism, pyrimidine metabolism, and ovarian steroidogenesis, which may be involved in the pathogenesis of primary dysmenorrhea. Compared with the model group, the torsion response, latency time and uterine organ coefficient of rats in the acupoint patch group were significantly improved, and nine uterine metabolites were significantly altered, among which metabolites such as 4-pyridoxic acid, d-glucarate and Phenol were identified as potential biomarkers for the therapeutic effects of GNGAP. Vitamin B6 metabolism, Ascorbate and aldarate metabolism and Tyrosine metabolism were enriched in nine metabolic pathways. These findings contribute to the screening study of potential pathological metabolic pathways in primary dysmenorrhea. Additionally, they reveal the biological effects of GNGAP in the treatment of primary dysmenorrhea at the metabolite level.

Project description:BackgroundPrimary dysmenorrhea is a common and often debilitating, gynaecological condition.ObjectiveTo investigate the effects of specific lifestyle variables on the prevalence and severity of primary dysmenorrhea.Materials and methodsA cross-sectional study of Jordanian women aged between 18-25 years old utilized a questionnaire as the main instrument of the study.ResultsPrimary dysmenorrhea was reported by 660 women out of 1988. It was found that approximately two thirds of them were students. Overall, 54.5% of the participants reported severe dysmenorrhea. A statistically significant correlation was found between severe dysmenorrhea and smoking at p value ˂0.001, sleeping less than 7 hours per 24 hours at p = 0.005, holding a university degree at p = 0.032, non-alcohol consumption at p = 0.044, frequent energy, fizzy, tea, coffee drinks and sugar intake. Interestingly, we found that severe dysmenorrhea was statistically significantly associated with women who never eat meat at p ˂0.001, cereals and fish consumers and with those who take less than 3 servings of fruit or none at all per week at p = 0.006. In addition to the previous variables, water intake of less than 1.0 litre a day, irregular cycles, non-OCP use and positive family history were found significantly associated with severe dysmenorrhea. Severe dysmenorrhea was significantly related to working less hours per week, higher stress level and longer bleeding duration at p = 0.021, 0.017 and 0.008, respectively. On the other hand, there was no statistically significant difference found between severe dysmenorrhea and the following variables: age, body mass index (BMI), weekly studying hours and age of menarche.ConclusionPrimary dysmenorrhea is prevalent in the Jordanian population. To overcome severe dysmenorrhea, women should increase their intake of fish and fresh fruits, drinking water and use of oral contraceptive pills. The study concluded that smoking, frequent sugar intake, fizzy drinks, coffee, tea and energy drinks were associated with severe dysmenorrhea. It is also worth mentioning that alcohol consumption had a positive impact on dysmenorrhea.Trial registrationRegistered in Clinicaltrial.gov (ID: NCT04583943).

Project description:BackgroundPrimary dysmenorrhea (PD) refers to functional dysmenorrhea, typically characterized by cyclical, pronounced lower abdominal pain and seriously affects a woman's work and quality of life. Some studies have reported that heat-sensitive moxibustion (HSM) is expected to alleviate the clinical symptoms. This systematic review aimed to evaluate the current evidence regarding the efficacy and safety of HSM on PD.Methods7 databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang Data Knowledge Service Platform (Wan Fang Data), and China Science and Technology Journal Database (VIP) were searched for clinical randomized controlled trials. Meanwhile, Revman 5.3 software was used to evaluate the methodological quality of the included literature. The confidence interval (CI) of either relative risk or mean difference was set to 95%. Besides, the heterogeneity of the research results is tested by I2.Results19 studies were ultimately included in this meta-analysis. All of them were declared as random controlled trials. 18 studies reported the total effective rate of the test group and the control group, which was significantly higher (RR: 0.92; 95% CI: 0.85,0.99; P=0.031 < 0.05) than the control group. It is demonstrated that the VAS score of the test group, totally 9 studies included, was significantly lower (SMD: -0.98; 95% CI: -1.15, -0.81; P < 0.001). The meta-analysis of 6 studies showed the symptom score of the test group was significantly lower (SMD: -0.67; 95% CI: -0.87, -0.47; P < 0.001). There were the CMSS results of 3 studies which were significantly lower (SMD: -0.88; 95% CI: -1.13, -0.62; P < 0.001). Combined with the results of subgroup analysis, compared with the control group, the test group had advantages in the VAS score, symptom score, and CMSS score.ConclusionsThe result has revealed the effectiveness and feasibility of HSM in treating PD, especially in improving the total effective rate and reducing the VAS score, symptom score, and CMSS score.

Project description:BackgroundPrimary dysmenorrhea (PD) is one of the most common gynecological conditions among young females, which has a significant negative impact on health-related quality of life and productivity. Despite its high prevalence, the evidence is limited regarding the management-seeking practices and its perceived effectiveness among females with PD.MethodsThis is a cross-sectional study conducted among 550 female students in six universities across Lebanon. The prevalence of PD, associated risk factors, and management-seeking practices were assessed using a self-administered questionnaire.ResultsThe prevalence of PD was 80.9%. Most of the females with PD described their menstrual pain as moderate (56%) to severe (34.6%), which significantly affected their daily activities and studying ability (P < 0.001). The major risk factors associated with PD included heavy menstrual flow (adjusted odds ratio [AOR] = 10.28), family history of PD (AOR = 2.52), history of weight loss attempt (AOR = 2.05), and medical specialization (AOR = 1.663). Only 36.9% of females with PD sought formal medical advice. Most dysmenorrheic females (76.4%) received medications for the management of PD, and remarkably none of them took hormonal contraceptives. Drugs commonly used for PD were mefenamic acid (26.2%), ibuprofen (25%), and paracetamol (11.5%), which were administered when the pain started (58.2%). All medications were significantly effective in reducing the pain score (P = 0.001), and most NSAIDs were more potent than paracetamol in managing PD (P = 0.001). However, no significant difference in adverse effects among medications was revealed. Moreover, no superiority of any individual NSAID for pain relief was established. Nevertheless, mefenamic acid was associated with the lowest risk of abdominal pain (OR: 0.03, P = 0.005) and the highest risk of flank pain (OR = 12, P = 0.02).ConclusionsSuboptimal management of PD is practiced among university students in Lebanon. Therefore, health care providers should educate dysmenorrheic females to optimize the self-management support of PD. Furthermore, future research is required to investigate females' misconceptions about hormonal contraceptives in the management of PD, aiming to raise awareness and correct misconceptions.

Project description:BackgroundThere are scanty data to apply radial extracorporeal shock wave therapy (rESWT) on the acupuncture points in the lower abdomen to reduce the menstrual pain. This trial aimed to test the rESWT safety and efficacy for treating primary dysmenorrhea (PD).MethodsForty-four young-women with PD were randomly assigned to one of the three groups: to receive rESWT on the acupuncture points during the follicular phase (Group A, n = 15) or during the luteal phase (Group B, n = 14), or to apply heat patch to the acupuncture points during the follicular phase as the control (Group C, n = 15) over three menstrual cycles. The pain severity (using 0-to-10 visual analog scale), the pain duration (hours), plasma PGF2α prostaglandin F2alpha and prostaglandin E2 (PGE2), self-rating anxiety scale and menstrual blood loss were assessed before and after interventions.ResultsThe pain severity and duration significantly decreased in all groups after interventions. Although the reduced pain duration was not different among the groups, the reduced pain severity was more significant (P = .003) in Groups A (-53.8 ± 33.7%) and B (-59.3 ± 36.7%) than in Group C (-18.7 ± 27.1%). The rESWT intervention did not change plasma prostaglandins in Group A, although there was a decreased prostaglandin F2alpha (-20.5 ± 32.9%) in Group B or a decreased PGE2 (-18.9 ± 17.8%) in Group C. The anxiety level showed no change after intervention. The menstrual blood volume reduced slightly after intervention and the change of menstrual blood loss in Group B was significant (P = .038).ConclusionThe rESWT applications on the abdominal acupuncture points safely and effectively reduced the menstrual pain, which was not associated with the prostaglandin changes. The rESWT-reduced pain seemed equally effective with the intervention applied during the follicular phase or luteal phase of the menstrual cycle. Heat patch placed on the abdominal acupuncture points also reduced the pain severity and duration, indicating that the improved blood flow could effectively alleviate the menstrual pain with PD. The changes in anxiety level and menstrual blood loss were slight after intervention.

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An in vivo mouse model of primary dysmenorrhea.

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An in vivo mouse model of primary dysmenorrhea.

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