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Objective To observe the analgesic effects of mild moxibustion on primary dysmenorrhea(PD)rats with cold and dampness stagnation syndrome and its effect on BDNF/TrkB signaling pathway in hypothalamus;To explore its mechanism for the treatment of PD.Methods A total of 32 Wistar non-pregnant female rats were randomly divided into blank group,model group,Western medicine group and mild moxibustion group,with 8 rats in each group.Except for the blank group,the other groups received estradiol benzoate intraperitoneal injection combined with ice bath treatment + oxytocin intraperitoneal injection to establish PD with cold and dampness stagnation syndrome model.The mild moxibustion group received treatment at"Shenque"and"Guanyuan"from the eighth day of modeling for 10 min,and the Western medicine group was given ibuprofen solution intragastically for 4 days.The latency period of rats twisting was observed and the twisting score was calculated,Western blot and PCR were used to detect the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue.Results Compared with the blank group,the model group showed a shortened latency period and an increased twisting score(P<0.01),the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Compared with the model group,the mild moxibustion group had a longer latency period and lower twisting score(P<0.01),while the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Conclusion Mild moxibustion may effectively improve the pain state of PD rats with cold and dampness stagnation syndrome.This mechanism may be related to downregulating c-fos expression,inhibiting BDNF/TrkB signaling pathway activation,thereby inhibiting pain signal transmission,regulating pain occurrence and maintenance.
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OBJECTIVE@#To observe the effects of electroacupuncture (EA) on NLRP3 inflammasome and its downstream protein gastermin D (GSDMD) in rats with primary dysmenorrhea (PDM), and to explore the potential mechanism of EA on the treatment of PDM.@*METHODS@#Forty healthy female SD rats without pregnancy were randomly divided into a control group, a model group, an EA group and an ibuprofen group, 10 rats in each group. PDM model was prepared by injection of estradiol benzoate and oxytocin. Except the control group, the rats in each group were subcutaneously injected with estradiol benzoate for 10 days, and oxytocin was injected on the 11th day. The rats in the EA group were intervened with EA (dense wave, frequency of 50 Hz) at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) at the same time of modeling, once a day, 20 min each time, for 10 consecutive days. The rats in the ibuprofen group were treated with 0.8 mL of ibuprofen by gavage (concentration of ibuprofen solution was 1.25 mg/mL) for 10 consecutive days. After modeling, the writhing reaction was observed. After intervention, the HE staining method was used to observe the histological morphology of uterus and evaluate the pathological damage score of uterus; ELISA method was used to detect the serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α); Western blot method was used to detect the protein expression of NLRP3, apoptosis related spot like protein (ASC), caspase-1, GSDMD, GSDMD-N and inflammatory factors (interleukin [IL]-1β, IL-18) in uterine tissue.@*RESULTS@#In the model group, a large number of vacuolar degeneration and death of endometrial epithelial cells, spiral arterioles congestion in lamina propria and neutrophil infiltration were observed. In the EA group, there was a small amount of vacuolar degeneration and death of endometrial epithelial cells, a small amount of spiral arterioles congestion in the lamina propria, and a small amount of neutrophils infiltration. In the ibuprofen group, there was very small number of degeneration and death of endometrial epithelial cells, and no obvious arterial congestion was found in lamina propria, and neutrophil infiltration was occasionally seen. Compared with the control group, in the model group the number of writhing was increased (P<0.01), the writhing reaction score and serum level of PGF2α and PGF2α/PGE2 value were increased (P<0.01), the level of PGE2 was decreased (P<0.01). Compared with the model group, in the EA group and the ibuprofen group the number of writhing were decreased (P<0.05), the latency of writhing was prolonged (P<0.01), the writhing reaction scores and serum levels of PGF2α and PGF2α/PGE2 values were decreased (P<0.05, P<0.01), the levels of PGE2 were increased (P<0.01). Compared with the control group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the uterine tissues of rats was increased in the model group (P<0.01). Compared with the model group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the uterine tissues of rats was decreased in the EA group and the ibuprofen group (P<0.01, P<0.05). There was no significant difference between the EA group and the ibuprofen group in the above indexes (P>0.05).@*CONCLUSION@#EA could alleviate pain and uterine tissue injury in rats with PDM. The mechanism may be related to the inhibition of the activation of NLRP3 inflammasome in rat uterine tissues, thereby inhibiting pyroptosis and its inflammatory factors release.
Subject(s)
Animals , Female , Pregnancy , Rats , Caspases , Dinoprost , Dinoprostone , Dysmenorrhea , Electroacupuncture , Ibuprofen , Inflammasomes , Interleukin-18 , NLR Family, Pyrin Domain-Containing 3 Protein , Oxytocin , Phosphate-Binding Proteins , Pyroptosis , Rats, Sprague-Dawley , UterusABSTRACT
Liquid chromatography-mass spectrometry was employed to analyze the chemical components in Curcuma longa tuberous roots(HSYJ), C. longa tuberous roots processed with vinegar(CHSYJ), and rat serum after the administration. The active components of HSYJ and CHSYJ absorbed in serum were identified based on the secondary spectrum of database and literature. The targets of primary dysmenorrhea was screened out from database. The protein-protein interaction network analysis, gene ontology(GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the common targets shared by the drug active components in serum and primary dysmenorrhea, and the component-target-pathway network was constructed. AutoDock was used to conduct molecular docking between the core components and targets. A total of 44 chemical components were identified from HSYJ and CHSYJ, including 18 absorbed in serum. On the basis of network pharmacology, we identified 8 core components(including procurcumenol, isobutyl p-hydroxybenzoate, ferulic acid, and zedoarondiol) and 10 core targets \[including interleukin-6(IL-6), estrogen receptor 1(ESR1), and prostaglandin-endoperoxide synthase 2(PTGS2)\]. The core targets were mainly distributed in the heart, liver, uterus, and smooth muscle. The molecular docking results showed that the core components were well bound to the core targets, indicating that HSYJ and CHSYJ may exert therapeutic effect on primary dysmenorrhea via estrogen, ovarian steroidogenesis, tumor necrosis factor(TNF), hypoxia-inducible factor-1(HIF-1), IL-17 and other signaling pathways. This study clarifies the HSYJ and CHSYJ components absorbed in serum, as well as the corresponding mechanism, providing a reference for further elucidating the therapeutic material basis and clinical application of HSYJ and CHSYJ.
Subject(s)
Female , Humans , Animals , Rats , Acetic Acid , Curcuma , Dysmenorrhea , Molecular Docking Simulation , Tumor Necrosis Factor-alpha , Cyclooxygenase 2ABSTRACT
ObjectiveTo compare the clinical effect of heat-sensitive moxibustion before menstruation and since the first day of menstruation on primary dysmenorrhoea (PD), thereby optimizing the clinical treatment plan. MethodsSixty patients with PD were randomly divided into pretreatment group (treated before menstruation) and conventional treatment group (treated since the first day of menstruation) of 30 cases each. For all patients, the area surrounded by bilateral Zigong (EX-CA1) and bilateral Guilai (ST 29) in the supine position, and that formed by bilateral Shenshu (BL 23) and Ciliao (BL 32) in the prone position were selected for circling moxibustion (2 min), sparrow-pecking moxibustion (1 min), and then moxibustion along the channels to stimulate the moxibustion sensation and obtain two heat-sensitive points with the best sensation for treatment. In the pretreatment group, moxibustion was applied 3-7 days before the onset of menstruation, and in the conventional treatment group, moxibustion was applied on the day of menstruation. Both groups were treated once daily for 7 days per menstrual cycle for 3 consecutive cycles. The clinical outcomes of the two groups were measured before and after treatment in terms of the COX menstrual pain symptom scale (CMSS) scores, visual analogue scale for pain (VAS) scores, and uterine artery hemodynamic indicators including blood pulsation index (PI) and resistance index (RI), and the clinical effect was compared. ResultsAfter treatment, the CMSS scores, VAS scores, PI and RI in the two groups decreased, and lower scores were found in the pretreatment group (P<0.05 or P<0.01). The total effective rate after treatment was 93.3% (28/30) in the pretreatment group, which was better than 73.3% (22/30) in the conventional treatment group (P<0.05). ConclusionThe clinical effect of heat-sensitive moxibustion before the menstruation for PD was better than that implemented since the first day of menstruation, by significantly improving the patients' dysmenorrhoea symptoms and uterine artery blood flow index.
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The mechanism of acupuncture in treating primary dysmenorrhea(PD)in rats was reviewed.The research on the mechanism of acupuncture in the treatment of PD involves endocrine,nervous,immune,metabolic and other aspects.However,the basic research did not actively pay attention to the clinical problems encountered in the treatment of PD by acupuncture and moxibustion,including the rule of point selection and the correlation mechanism between acupoints and uterus in the treatment of PD by acupuncture and moxibustion,the key technical parameters of the treatment of PD by acupuncture and moxibustion and the rule of the action of acupuncture and moxibustion.The basic research of acupuncture treatment of primary dysmenorrhea should pay attention to translational medicine.
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Objective To evaluate the efficacy and safety of saffron freeze-dried effervescent tablets in the treatment of primary dysmenorrhea of qi stagnation and blood stasis,and to provide reference for its clinical application.Methods A prospective,randomized,double-blind,placebo parallel controlled clinical trial was designed.60 patients were randomly divided into treatment group and control group.After 3 months of elution,the patients were treated with saffron freeze-dried effervescent tablets and placebo respectively for 2 menstrual cycles and were followed up for 2 months.Results There was no significant change in the control group before and after treatment,while the symptoms in the treatment group were significantly relieved after treatment,which were significantly different from those before treatment,and no adverse reactions occurred in all subjects.Conclusion Saffron freeze-dried effervescent tablets can effectively treat primary dysmenorrhea of qi stagnation and blood stasis with good long-term efficacy and safety,which is worthy of further clinical study.
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Aim To explore its potential biological basis and the endogenous metabolic characteristics of urine during the formation of primary dysmenorrhea via untargeted urine metabolomics. Methods Twenty SD rats were randomly divided into control group and model group. The primary dysmenorrhea model was reproduced by estradiol benzoate combined with oxytocin, and the contrrol group took food and water freely. The differential metabolites and core metabolic pathways were found by multivariable pattern recognition method combined with ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry. The receiver operating characteristic ( ROC ) curve was drawn by metaboanalyst 5.0 platform to evaluate the clinical diagnostic efficacy of core metabolites. Results A total of 46 metabolites with significant differences, such as hippuric acid, phenylacetaldehyde, prostaglandin G2, 6-hydroxy-5-methoxyindole glucuronide, were screened, mainly involving phenylalanine metabolism, pentose and glucuronate interconversions, and arachidonic acid metabolism. ROC curve showed that the area under the curve of four core biomarkers was greater than 0.7. Conclusions Different metabolic maps are presented in different progressive stages of primary dysmenorrhea, mainly involving the disorders of fatty acid metabolism, carbohydrate metabolism and amino acid metabolism. Meanwhile, the extracted characteristic bi¬omarkers have high diagnostic value for the evaluation of primary dysmenorrhea.
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OBJECTIVE@#To observe the skin surface microcirculation of acupoints of conception vessel, governor vessel and thoroughfare vessel in patients with primary dysmenorrhea using laser speckle contrast imaging (LSCI), and provide acupoint selection basis of acupuncture-moxibustion for primary dysmenorrhea.@*METHODS@#Ninety-nine healthy female college students with regular menstrual cycles (normal group) and 94 female college students with primary dysmenorrhea (dysmenorrhea group) were recruited. Before menstrual period, on the first day of menstruation, and on the third day after menstruation, LSCI was used to observe the surface microcirculation at the abdominal acupoints of conception vessel, i. e. Yinjiao (CV 7), Qihai (CV 6), Shimen (CV 5), Guanyuan (CV 4), Zhongji (CV 3) and Qugou (CV 2), acupoints of thoroughfare vessel, i. e. Huangshu (KI 16), Zhongzhu (KI 15), Siman (KI 14), Qixue (KI 13), Dahe (KI 12), Henggu (KI 11) and acupoints of lumbosacral region of governor vessel, i. e. Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3), Yaoshu (GV 2) as well as two non-acupoints.@*RESULTS@#Before menstrual period, there was no significant difference in the surface blood perfusion of the acupoints between the dysmenorrhea group and the normal group (P>0.05). On the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) and right Huangshu (KI 16) in the dysmenorrhea group was higher than that in the normal group (P<0.05, P<0.01). On the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) in the dysmenorrhea group was lower than that in the normal group (P<0.05).@*CONCLUSION@#In patients with primary dysmenorrhea, on the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) of governor vessel, and the right Huangshu (KI 16) of thoroughfare vessel is increased, while on the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) of thoroughfare vessel is decreased. These findings might provide a basis for acupoint selection in the acupuncture-moxibustion treatment of primary dysmenorrhea.
Subject(s)
Humans , Female , Microcirculation , Dysmenorrhea/therapy , Menstrual Cycle , Acupuncture Points , Acupuncture TherapyABSTRACT
This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E_2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E_2(PGE_2), prostaglandin F_(2α)(PGF_(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E_2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE_2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF_(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P<0.05 or P<0.01), significantly reduce the uterine and ovarian coefficients(P<0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE_2 content was significantly increased(P<0.05), COX-2, PGF_(2α) and Ca~(2+) content, and PGF_(2α)/PGE_2 was significantly decreased(P<0.05 or P<0.01), and OT content was decreased, while E_2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P<0.05 or P<0.01) and ERα protein expression was upregulated(P<0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P<0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.
Subject(s)
Humans , Rats , Female , Animals , Estrogen Receptor alpha , Oxytocin , Dysmenorrhea/metabolism , Cyclooxygenase 2 , Dinoprostone , RNA, Messenger/metabolism , DinoprostABSTRACT
BACKGROUND@#The placebo response of sham acupuncture in patients with primary dysmenorrhea is a substantial factor associated with analgesia. However, the magnitude of the placebo response is unclear.@*OBJECTIVE@#This meta-analysis assessed the effects of sham acupuncture in patients with primary dysmenorrhea and the factors contributing to these effects.@*SEARCH STRATEGY@#PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were searched from inception up to August 20, 2022.@*INCLUSION CRITERIA@#Randomized controlled trials (RCTs) using sham acupuncture as a control for female patients of reproductive age with primary dysmenorrhea were included.@*DATA EXTRACTION AND ANALYSIS@#Pain intensity, retrospective symptom scale, and health-related quality of life were outcome measures used in these trials. Placebo response was defined as the change in the outcome of interest from baseline to endpoint. We used standardized mean difference (SMD) to estimate the effect size of the placebo response.@*RESULTS@#Thirteen RCTs were included. The pooled placebo response size for pain intensity was the largest (SMD = -0.99; 95% confidence interval [CI], -1.31 to -0.68), followed by the retrospective symptom scale (Total frequency rating score: SMD = -0.20; 95% CI, -0.80 to -0.39. Average severity score: SMD = -0.35; 95% CI, -0.90 to -0.20) and physical component of SF-36 (SMD = 0.27; 95% CI, -0.17 to 0.72). Studies using blunt-tip needles, single-center trials, studies with a low risk of bias, studies in which patients had a longer disease course, studies in which clinicians had < 5 years of experience, and trials conducted outside Asia were more likely to have a lower placebo response.@*CONCLUSION@#Strong placebo response and some relative factors were found in patients with primary dysmenorrhea. PROSPERO registration number: CRD42022304215. Please cite this article as: Sun CY, Xiong ZY, Sun CY, Ma PH, Liu XY, Sun CY, Xin ZY, Liu BY, Liu CZ, Yan SY. Placebo response of sham acupuncture in patients with primary dysmenorrhea: A meta-analysis. J Integr Med. 2023; 21(5): 455-463.
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Female , Humans , Dysmenorrhea/therapy , Acupuncture Therapy , Pain Management , Needles , Placebo EffectABSTRACT
BACKGROUND@#Primary dysmenorrhea (PD) is the most common complaint associated with menstruation and affects up to three-quarters of women at some stage of their reproductive life. In Chinese medicine, navel therapy, treatment provided at Shenque (CV 8), is used as a treatment option for PD.@*OBJECTIVE@#To evaluate the effect of navel therapy on pain relief and quality of life in women with PD, compared with Western medicine (WM).@*METHODS@#China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), SinoMed and Wanfang Database, MEDLINE, the Cochrane Library, Embase, Web of Science, and the International Clinical Trial Registry of the U.S. National Institutes of Health were searched from their inceptions to April 1, 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of navel therapy on PD were eligible for inclusion. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool.@*RESULTS@#Totally 24 RCTs involving 2,614 participants were identified. Interventions applied to acupuncture point CV 8 included: herbal patching, moxibustion or combined navel therapy (using at least 2 types of stimulation). Compared to placebo, there was a significant effect in favor of navel therapy on reducing overall menstrual symptom scores at the end of treatment [mean difference: -0.82, 95% confidence interval (CI): -1.00 to -0.64, n=90; 1 RCT]. As compared with Western medicine, navel therapy had a superior effect on pain intensity as assessed by Visual Analogue Scale at the end of treatment [standardized mean difference (SMD): -0.64, 95% CI: -1.22 to -0.06, I2=80%, n=262; 3 RCTs]; on symptom resolution rate at 3-month follow-up (risk ratio: 1.94, 95% CI: 1.47 to 2.56, n=1527, I2=38%; 13 RCTs); and on global menstrual symptoms score at the end of treatment (SMD: -0.67, 95% CI: -0.90 to -0.45, I2=63%, n=990; 12 RCTs). Subgroup analyses showed either a better or an equivalent effect comparing navel therapy with Western medicine. No major adverse events were reported. The methodological quality of included trials was poor overall.@*CONCLUSIONS@#Navel therapy appears to be more effective than Western medicine in decreasing menstrual pain and improving overall symptoms of PD. However, these findings need to be confirmed by well-designed clinical trials with adequate sample size (Systematic review registration at PROSPERO, No. CRD42021240350).
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Female , Humans , United States , Dysmenorrhea/drug therapy , Medicine, Chinese Traditional , Randomized Controlled Trials as Topic , Moxibustion , Pain ManagementABSTRACT
Background: Primary dysmenorrhea (PD) affects adolescent girls within 2 years of menarche and roughly 16–91% suffer from it, heavily incapacitating their educational and social life. Elevated prostaglandins (PG’s), especially PGF2? is alleged to be the culprit behind PD but the prevalence continues to remain variable across various geographical domains. Aim and Objectives: The aim of the study was to ascertain the prevalence of PD and to determine the association between PD and body mass index (BMI). Materials and Methods: A cross-sectional study 250 randomly selected adolescent girls was conducted across different government and private schools of Hyderabad. The participants were asked to fill a self-administered questionnaire which included sociodemographic details, anthropometric measurements, and complete menstrual history including the prevalence and severity of PD. Participants were segregated into four groups according to the Revised IAP BMI charts and the intensity of pain was scored by Numerical Pain Rating Scale. Results: The prevalence of PD was estimated to be 70% with 34.7% complaining of severe PD. About 42.4% participants reported to suffer from PD, a day before menstrual flow and the most commonly associated symptoms were nausea and fatigue. About 52.68% participants suffered from PD every month. While assessing the impact of BMI on PD, the prevalence and severity of PD were found higher in overweight and obese participants and the difference was statistically significant. Lower age of menarche, longer cycles, and heavier flow were associated with increased risk of PD. Conclusion: PD is physically and emotionally challenging and as rising adolescent obesity is a correctible predisposing factor, there is an urgent need to acknowledge the issue.
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Dysmenorrhea, one of the most prevalent gynaecological problems in young women, particularly among teenagers, characterized by painful menstruation severe enough to prevent a person from doing day-to-day activities. It is the main factor behind young women's missed job and school days of teenagers. Primary dysmenorrhea is widely prevalent in more than 70% of teenagers and 30 -50% of menstruating women. Among Yonirogas, Udavarta yonivyapat is a condition characterized by painful menstruation and the relief of discomfort following blood discharge, which is typical of primary dysmenorrhea. In modern medical science, various forms of treatments are available for the relief of Primary dysmenorrhea which includes antispasmodic, analgesics, prostaglandin synthesis inhibitors, hormonal therapy etc. Reluctance of young girls and ladies to adopt the hormone therapies bring them to Ayurvedic treatment or any other alternative treatment of their choice. Ayurvedic management aims at vatanulomana through Snehana, Swedana, Vasti along with Samana oushadha which can alleviate Vata. Abhayatrivrudadi kashaya mentioned in the context of Udavarta chikitsa from Chikitsa manjari consists of Abhaya, Trivrut, Kulatha, Pippali and Eranda taila. Properties of this yoga include Vatanulomana, Sulaghna and Udavartahara. An 18 year old girl complained with severe pain during menstruation, low back ache, nausea and vomiting came to the OPD of Prasutitantra & Streeroga, Government Ayurveda College, Tripunithura is taken for this study. It is evident from the case study that Abhayatrivrudadi kashaya is effective in the management of primary dysmenorrhea.
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While the role of prostaglandin as a trigger in dysmenorrhea is well known, not many are aware that inflammation and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome are also implicated in primary dysmenorrhea (PD). Inhibition of NLRP3 inflammasome and inflammation pathways is an important approach to treating dysmenorrhea and also the symptoms of premenstrual syndrome. Mefenamic acid is an effective and selective inhibitor of the NLRP3 inflammasome, which can be considered the most important option for PD treatment owing to its action via various pathways. In this article, the authors have reviewed the role of inflammation and NLRP3 inflammasome in causing PD, how inhibitors of NLRP3 inflammasome can treat dysmenorrhea and the mechanism of action of mefenamic acid as NLRP3 inflammasome inhibitor and its role in PD.
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Despite being one of the most common gynecological issues faced by women of reproductive age, dysmenorrhea largely remains an ignored, underdiagnosed and untreated condition. It continues to be a public health issue and has a significant impact on the quality of life of the affected women in terms of inability to lead routine activities, absenteeism from academic activities or work and reduced social activities. Currently, existing evidence correlates and implicates the excessive synthesis of prostaglandins with the menstrual pain. Hence, treatment approaches that can inhibit prostaglandins' production or already formed prostaglandins can provide relief in dysmenorrhea. In this review, the impact of dysmenorrhea on the quality of life of women, the role of prostaglandins in the pathogenesis of dysmenorrhea, and how nonsteroidal anti-inflammatory drugs (NSAIDs) like mefenamic acid can be safe and effective in managing dysmenorrhea are discussed.
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Dysmenorrhea is a common gynecological disease in clinic, with primary dysmenorrhea and secondary dysmenorrhea. Primary dysmenorrhea is usually not accompanied by organic lesions in genital organs, which is mainly related to the increase of prostaglandin content in endometrium during menstruation. Secondary dysmenorrhea is accompanied by organic lesions of reproductive organs, often associated with local lesions of reproductive organs, but also with patients' mental factors and neuroendocrine factors.The incidence of dysmenorrhea is as high as 73.8%, and there is no radical cure method, which has a great impact on the life, work and learning of patients. Chinese medicine essential oil widely exists in aromatic Chinese medicine, with antibacterial, antioxidant and anticancer activities. It can regulate neuroendocrine function, anti-inflammatory and analgesic effects, and improve mood by regulating the levels of prostaglandins, oxytocin and other hormones in the body and regulating the emotions of patients, there by alleviating dysmenorrhea to a certain extent. In recent years, many scholars have made more in-depth research on Chinese medicine essential oil in alleviating dysmenorrhea, but there is a lack of comprehensive collation of such studies. In this regard, the author has systematically sorted out the generation and classification of dysmenorrhea, the mechanism of action of essential oil of traditional Chinese medicine to alleviate dysmenorrhea and the application of essential oil of traditional Chinese medicine in the field of dysmenorrhea by consulting relevant literature in Chinese and foreign languages in recent years, so as to provide reference for the treatment of dysmenorrhea.
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OBJECTIVE@#To prove the therapeutic effect of auricular intradermal needling and auricular point sticking on primary dysmenorrhea (PD), and to explore its mechanism.@*METHODS@#A total of 90 patients with PD were randomized into an auricular intradermal needling group, an auricular point sticking group and a placebo group, 30 cases in each one. Neishengzhiqi (TF@*RESULTS@#Compared before treatment, the scores of CMSS, VAS and SAS were decreased at each time point of treatment in the auricular intradermal needling group, 2, 3 courses into treatment and at follow-up in the auricular point sticking group and 3 courses into treatment in the placebo group (@*CONCLUSION@#Auricular intradermal needling and auricular point sticking can both improve the clinical symptom of primary dysmenorrhea, relieve the pain and anxiety, their mechanism may be related to regulating the serum levels of PGF
Subject(s)
Female , Humans , Acupuncture Points , Acupuncture, Ear , Anxiety Disorders , Dysmenorrhea/therapy , Treatment OutcomeABSTRACT
Objective:To study the effect of Wenjing Huayu Zhitong therapy (Xiangyan Zhitong prescription, XZP) on the mitogen activated protein kinase (MAPK)/extracelluar regulated protein kinase (ERK) signaling pathway of primary dysmenorrhea (PD) rats, and explore the pathogenesis of PD and the mechanism of action of Wenjing Huayu Zhitong therapy. Method:Forty-eight female SPF-grade Wistar rats were randomly divided into blank group,model group, western medicine group, low-dose XZP group, medium-dose XZP group, and high-dose XZP group, with 8 rats in each group. In addition to the blank group, dysmenorrhea rat model with cold coagulation and blood stasis syndrome was established by cold stimulation combined with estradiol benzoate and oxytocin. The rats in the blank group,model group,western medicine group, low-dose XZP group, medium-dose XZP group, and high-dose XZP group were given distilled water, distilled water,0.06 g·kg<sup>-1</sup> ibuprofen, 6.55 g·kg<sup>-1</sup> XZP, 13.09 g·kg<sup>-1</sup> XZP, and 26.18 g·kg<sup>-1</sup> XZP, respectively, by gavage for 6 days. The writhing latency and writhing frequency of rats were recorded within 30 min after oxytocin injection.Western blot was used to detect the protein expression of B-Raf, mitogen activates extracellular regulated kinases1/2 (MEK1/2), extracellular regulated kinases1/2 (ERK1/2), p-MEK1/2, p-ERK1/2, c-Jun, and cyclooxygenase-2 (COX-2) in rat uterus. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to detect the mRNA expression of B-Raf, MEK1, MEK2, ERK1, ERK2, c-Jun, and cyclooxygenase-2 (COX-2) in rat uterus. Result:Compared with the model group,the treatment groups showed insignificantly prolonged writhing latency and significantly reduced writhing frequency (<italic>P</italic><0.01). On the 6<sup>th</sup> day of modeling, there was no significant difference in the quantitative scores of symptoms and signs among the treatment groups. On the 12<sup>th</sup> day of modeling, the scores changed little in the western medicine group and the low-dose XZP group and decreased significantly in the medium- and high-dose XZP groups (<italic>P</italic><0.01) compared with those in the model group. Compared with those in the blank group, the protein and mRNA levels of p-MEK1/2, p-ERK, B-Raf, c-Jun, and COX-2 in the model group were significantly up-regulated (<italic>P</italic><0.01). Compared with those in the model group, the protein and mRNA levels of p-MEK1/2, p-ERK1/2, B-Raf, c-Jun, and COX-2 in the western medicine group, medium-dose XZP group, and high-dose XZP group were significantly down-regulated (<italic>P</italic><0.05,<italic>P</italic><0.01). Conclusion:The mechanism of Wenjing Huayu Zhitong therapy in treating PD with cold coagulation and blood stasis syndrome may be related to the down-regulation of MAPK/ERK signaling pathway.
ABSTRACT
Objective:To evaluate the analgesic effects of Wenjing Zhitong prescription (WZP) and explore its possible analgesic mechanisms so as to provide experimental basis for research and development of new Chinese medicine. Method:Analgesic effects of WZP were evaluated by observing the writhing latency and number in the writhing models which were induced by oxytocin in rats as well as those induced by acetic acid and prostaglandin E<sub>1</sub> (PGE<sub>1</sub>), respectively in mice. Effect of WZP on uterine contraction frequency, amplitude and activity were evaluated by observing the oxytocin-induced contraction of uterine smooth muscle in rats and rabbits <italic>in vivo</italic>. In the oxytocin-induced rat writhing models, the content of prostaglandin F<sub>2</sub><italic><sub>α </sub></italic>(PGF<sub>2</sub><italic><sub>α</sub></italic>) and prostaglandin E<sub>2 </sub>(PGE<sub>2</sub>) in rat uterine tissues and the content of beta-endorphins (<italic>β</italic>-EP) in rat serum were detected by enzyme-linked immunosorbent assay (ELISA). Expression of estrogen receptor (ER) and oxytocin receptor (OTR) in rat uterine were tested by Real-time polymerase chain reaction(Real-time PCR) method to investigate the possible molecular mechanism of WZP for its analgesic effect. Result:Results of analgesic effect showed that in oxytocin-induced rat writhing experiment, the number of writhing responses in both the WZP (1.5,3.0 g·kg<sup>-1</sup>) group was lower than than in the model group (<italic>P</italic><0.05). In acetic acid-induced mice writhing experiment, the latency of writhing response in WZP (6.0 g·kg<sup>-1</sup>) group was significantly prolonged as compared with that in model group <italic>(P</italic><0.01), and the number of writhing response was significantly reduced (<italic>P</italic><0.05). In PGE<sub>1</sub>-induced mice writhing model, the writhing number in WZP (1.5,3.0,6.0 g·kg<sup>-1</sup>) groups was significantly lower than that in the model group (<italic>P</italic><0.05,<italic>P</italic><0.01). Results of effect on uterine smooth muscle demonstrated that WZP (0.38,0.75,1.50 g·kg<sup>-1</sup>) could significantly reduce the frequency of uterine smooth muscle contraction in rabbits (<italic>P</italic><0.05,<italic>P</italic><0.01), WZP (0.75,1.50,3.00 g·kg<sup>-1</sup>) could significantly reduce the contractile amplitude and activity of smooth muscle in the uterus of rats (<italic>P</italic><0.05). Results of molecular mechanisms of analgesic effects showed that the WZP (0.75,1.50,3.00 g·kg<sup>-1</sup>) significantly reduced the content of PGF<sub>2</sub><italic><sub>α</sub></italic> and the ratio of PGF<sub>2</sub><italic><sub>α</sub></italic> to PGE<sub>2</sub> in the uterine tissue of rats (<italic>P</italic><0.01). In the WZP (3.00 g·kg<sup>-1</sup>) group, the levels of <italic>β</italic>-EP in the serum of rats were significantly increased (<italic>P</italic><0.01), and the levels of OTR in uterus of rats in the WZP (1.50,3.00 g·kg<sup>-1</sup>) group were significantly decreased (<italic>P</italic><0.05). Conclusion:Pharmacological studies demonstrated potent analgesic effect of WZP, and such analgesic effect were mediated by significantly inhibiting contraction of uterine smooth muscle, decreasing the contents of PGF<sub>2</sub><italic><sub>α</sub> </italic>and ratio of PGF<sub>2</sub><italic><sub>α</sub></italic>/PGE<sub>2</sub>, reducing OTR expression in uterine as well as increasing the amount of <italic>β</italic>-EP in serum.
ABSTRACT
This study aimed to explore the characteristic role of Puerariae Lobatae Radix(PLR) in Gegen Decoction for the treatment of primary dysmenorrhea(PD). Estrogen(E_2) was combined with oxytocin to establish a mouse model of PD. The mice were randomly divided into a normal group, a model group, a Gegen Decoction group, a PLR-free Gegen Decoction group, a PLR group, and a positive drug group(ibuprofen). Writhing response times and writhing incubation of mice in each group were tested by behavio-ral assessment, and the serum levels of prostaglandin F_(2α)(PGF_(2α)), prostaglandin E_2(PGE_2), E_2, and progesterone(PROG) were detected by ELISA kits. Western blot method was adopted to detect cyclooxygenase-2(COX-2) and estrogen receptor alpha(ER_α) expression levels in uterine tissues. Doppler ultrasound was employed to detect changes in uterine artery blood flow in mice, including peak systolic blood flow velocity(maximum velocity), end-diastolic velocity(minimum velocity), peak systolic blood flow velocity/end-diastolic velocity(S/D), pulsatility index(PI), and resistive index(RI). Histopathological changes in the uterus were detected by HE staining. Based on the oxytocin-induced isolated uterine contraction model, the effects of Gegen Decoction, PLR-free Gegen Decoction, and PLR on the amplitude, frequency, and activity of isolated uterine contraction were compared to investigate the role of PLR in Gegen Decoction for the treatment of PD. The results showed that compared with the Gegen Decoction group, the PLR-free Gegen Decoction improved the indicators of PD except for E_2 content, ER_α expression, and uterine artery blood flow. PLR could significantly down-regulate the serum content of E_2 and the protein expression of uterine ER_α, and improve the uterine artery blood flow. The data suggested that PLR, as the sovereign drug of Gegen Decoction, might function in Gegen Decoction for the treatment of PD by mediating E_(2 )and improving the uterine artery blood flow.