| Dysmenorrhea is the spasmodic pain of lower abdomen and waist on women of reproductive age during the menstrual flow and before or after the menstruation,some severely associated symptoms maybe headache,nausea,vomiting or extreme chilliness.It is commonly divided into primary dysmenorrhea and secondary dysmenorrhea.Primary dysmenorrhea is characteristically starts at the sixth month after menarche,and no macroscopically identifiable pelvic pathology.The secondary dysmenorrhea with an identifiable pathological condition of reproductive system that caused by genital inflammation,uterine fibroids or uterine endometriosis.Dysmenorrhea is the most common gynecologic complaint,having a strong impact on women’s daily life and living quality.Its pathogenic factors are complex.The pathological changes are mainly to the strong contraction,ischemia and hypoxia of uterine smooth muscle and uterine wall spiral arteries.Modern medicine is generally considered that the dysmenorrhea is closely related to the following factors.First:The change of prostaglandin（prostaglandin,PGs）,is considered to be the fundamental mechanism of dysmenorrhea.Studies have shown that the uterus muscle cells is not only the PGs target cells,but also produce various PGs substances that involved in the regulation uterine muscle cells’s contraction and relaxation.PGE2 can easily cause infection,increasing the sensitivity of pain of the nerve endings.Endometrial PGs in women with dysmenorrhea are significantly higher than in normal women,whether the proliferative phase or secretory phase.Studies have shown that women suffering from dysmenorrhea have a higher level of PGE2.The high level of PGE 2 will increase pain,and associate with a range of clinical symptoms:severe abdominal pain,nausea,vomiting,low blood pressure,paleness,diarrhea or constipation,fainting,mild headache,fatigue,forgetfulness,etc.In PGs family,PGE2 is an important mediator that induces inflammation and pain,producing a wide-ranging and long-lasting vasodilatory effects and pain,also associating with hyperalgesia.Second:Dysmenorrhea is related with the changing levels of sex hormone during the menstrual cycle.The peak level of estrogen during the mid-luteal increase the concentration of endometrium PGs in pre-menstrual.PGs in the peripheral blood and uterine of dysmenorrhea rat model are closely related with the concentration of the estradiol（estrogen 2,E 2）.Third:Dysmenorrhea is closely related to β-endorphin（β-EP）.β-EP is a class of neural peptides with morphine-like activity and an endogenous analgesic effect,participating in the regulation of reproductive endocrinology,and plays an important role in the regulation of the hypothalamic-pituitary functions.β-EP is constrainted by sex hormones,but progesterone can significantly improve the secretion of β-EP,and estradiol suppresses effect of progesterone on β-EP.Therefore,the reduction level of β-EP during luteal phase leading to disordered uterine activity is considered to be one of the reasons of dysmenorrhea.Epidemiological studies have shown that primary dysmenorrhea is the most common gynecological diseases,sample survey showed that there was 33.1%women suffered dysmenorrhea in China,which accounted for 53.2%of primary dysmenorrhea,seriously impact on work are for 13.55%.In Canadian,researchers found that 60%of women are with moderate to severe primary dysmenorrhea,among which 51%of dysmenorrhea women’s daily lives are affected,and 17%of patients with severe dysmenorrhea dysmenorrhea have to absent from work or school.In Malaysia,one epidemiological study for the 12-19 year-old girls at secondary showed that about 69.4%of the girls had experienced primary dysmenorrhea.Therefore,the emphasis on the treatment of dysmenorrhea is necessary.Non-steroidal anti-inflammatory drugs are the most commonly used drugs in the clinical treatment of primary dysmenorrhea,about 64%to 100%of person relieve subjective symptoms after application of these drugs.NSAIDs reduce the biological synthesis of PGs by means of inhibition of cyclooxygenase-2（Cycloxygenase-2,COX-2）,relieving spastic contraction of the uterus caused by PGs.With other drugs,it can enhance the analgesic effect.COX has two types of isoenzymes,COX-1 and COX-2,traditional NSAIDs have poor selectivity of two enzymes,thus it easily cause a series of side effects of gastrointestinal and central nervous system.NSAIDs include aspirin,Fenbid,sulfuric acid,paracetamol,acetaminophen,indomethacin,indomethacin,etc.,they have an efficiency of 30%to 80%,but will cause more side effects of gastrointestinal and central nervous system.In the middle and late 1990s,selective COX-2 inhibitors,such as meloxicam,MK966,and a new generation of NSAIDs have been developed to market,although reducing gastrointestinal side effects,the expensive price and surviving side effect limit its universal application.Parecoxib sodium is a highly selective COX-2 inhibitor,it can be quickly hydrolyzed to valdecoxib[4-（5-methyl-3-benzeneisoxazole-4-yl）benzenesulfonamide]by liver carboxylic acid esterase after intravenous injection.Valdecoxib is a highly selective COX-2 inhibitor,participating in PGs synthesis process,its anti-inflammatory and analgesic effects are exerted by means of specificly inhibiting COX-2 and blocking PGs synthesis of arachidonic acid.A large number of clinical studies have shown that parecoxib sodium has a good postoperative analgesic effect on gynecology,orthopedics,general surgery,neurosurgery and other surgeries,having fewer adverse reactions,and reducing the dosage of opioids.The application of parecoxib sodium is not only use to treat the postoperative pain,also clinical trials show that,before the surgery,use parecoxib can significantly reduce postoperative pain VAS score,improve the rate of patients’ satisfaction,and reduce postoperative dosage of other narcotic analgesics.In this study,we use oxytocin and estradiol benzoate to produce dysmenorrhea rat model.The theory is:estrogen can increase the sensitivity of the uterine muscle to oxytocin,and oxytocin can cause uterine muscle contraction in the female rats,resulting in cramps.After injecting oxytocin,female rats turn up with abdominal contraction,torso and hind legs stretched,and internal rotation of the hip and limb;it means "contorted" reaction.The method of oxytocin-induced dysmenorrhea model is simple and reproducible,in our country a large part of dysmenorrhea study chose oxytocin-induced dysmenorrhea model,so dose this experiment.With this model,we study the effect of parecoxib sodium,a non-steroidal anti-inflammatory drug,on the dysmenorrhea rat model,and also study the impact of parecoxib sodium on the model rats’ pain threshold,serum inflammatory cytokines,and substances such as COX-2,PGE2,β-EP in the endometrial,braincingulate and frontal cortex organizations.It will provide experimental basis for clinical application of parecoxib sodium to treat primary dysmenorrhea.Materials and methods1.Animals 48 female wistar rats,weight 180-200g,were provided by the Experimental Animal Center of Southern Medical University.Feeding conditions:conventional animal experiment room,5 rats per cage,feeding 2 days before the operation,by hand feeding and management.12 hours lighting for animal room,good ventilation and air condition,temperature control at 25 ± 1℃ relative humidity 40-50%.Regular laboratory disinfection.2.Animal groups Wistar rats were randomly divided into four groups,12 of each group.The animal groups and treatment factors were:①Group C:Control②Group M:Primary dysmenorrhea model③Group A:Primary dysmenorrhea model+ preemptive analgesia of parecoxib sodium（30 minutes before surgery）④ Group B:Primary dysmenorrhea model+ preemptive analgesia of parecoxib sodium（3 days before surgery）3.Establishment of primary dysmenorrheal rat modelThe primary dysmenorrheal rat model was established by referring the book of animal models commonly used in medical research.Unpregnancy female Wistar rats,weight 180-220g,were treated with estradiol（E2）by subcutaneous injection for consecutive 10 days(the 1st and the 10th day 0.5mg/day,the 2nd to 9th day 0.2mg/day).In the 10th day,rats were injected with oxytocin 2U intraperitoneally after treated with E2 for 45minutes.And then we could observe writhing response in rats induced by oxytocin in 30 minutes.Group C:Wistar rats were treated with normal sodium as a negative contral by subcutaneous injection for consecutive 10 days(the 1st and the 10th day 0.25ml/day,the 2nd to 9th day 0.1ml/day).Group M:Wistar rats were treated with estradiol benzoate（2mg/ml）by subcutaneous injection for consecutive 10 days(the 1st and the 10th day 0.5mg/day,the 2nd to 9th day 0.2mg/day).In the 10th day,rats were injected with oxytocin 2U intraperitoneally after treated with E2 for 45minutes.The writhing response could be observed in rats induced by oxytocin in 30 minutes.Group A:Wistar rats were treated with estradiol benzoate by subcutaneous injection for consecutive 10 days(the 1st and the 10th day 0.5mg/day,the 2nd to 9th day 0.2mg/day).In the 10th day,rats were injected with oxytocin 2U intraperitoneally after treated with E2 for 45minutes.The writhing response could be observed in rats induced by oxytocin in 30 minutes.Parecoxib（0.72mg/kg）were administrated to rats half an hour before operation.Group B:Wistar rats were treated with estradiol benzoate by subcutaneous injection for consecutive 10 days(the 1st and the 10th day 0.5mg/day,the 2nd to 9th day 0.2mg/day).In the 10th day,rats were injected with oxytocin 2U intraperitoneally after treated with E2 for 45minutes.The writhing response could be observed in rats induced by oxytocin in 30 minutes.Parecoxib（0.72mg/kg）were administrated to rats 3 days of preoperation.4.Pain threshold measurement A potassium-ion density dolorimeter（model EP601C）attained from Scientific and Teaching Instruments Factory of East China Normal University was performed to measure the pain threshold in rats.Prior to measuring,the measuring site in the subjects should be covered and rubbed with conductive paste,which reduced the skin resistance and promoted skin permeability,resulting in an electric current conveying easier.Fistly,a piece of gauze patch was cut according to the size of reference electrode slice（cathode,in black）and wet out by saturated potassium chloride.Secondly,base of the rat’s tail was wrapped up by the wet gauze and tied in the reference electrode slice.Thirdly,cotton,wet out by saturated potassium chloride,was plugged into the hole of the active electrode（anode,in red）.After all the things had been ready,we switched on the power and put the active electrode on the measuring site left hind limb.At the same time we observed the rat tail flick latency.When the rat flick its tail,the current value on the dial was recorded as pain threshold.Pain threshold was measured every 5 minutes,3 times in all,and then written by average.5.Recording the number of writhes in ratsIn the 10th day,rats were injected with oxytocin 2U intraperitoneally after treated with E2 for 45 minutes.If primary dysmenorrheal rat model was established successfully,we could observe a contraction of the abdominal muscles together with a stretching the hind limb,and an internal rotation on one side of the body.The number of writhes occurring in 30 minutes after injection of the inducing agent was counted for each animal and a mean calculated for each group.6.Cecal resectionAll the rats were arranged to fast but normal drinking during preoperative for 12 hours.The next day,each rat was weighted and anesthetized by intraperitoneal injection of 20%urethane（5 ml/kg）and fixed on the board on supine position.The temperature of rats was controlled at（35 ± 1）℃ by using a heat lamp.Then we could do a cecal resection according to the following operating procedures:preoperative preserved skin in abdomen→sterilizing→draping sterile surgical towels→incising the skin,muscle,peritoneum along with Hunter’s line→finding the cecum carefully→separating and ligating the vessels between the cecum and the small intestine→ligating and resecting the cecum→suturing the peritoneum,muscle and skin respectively.7.Quantitative measurements of E2,TNF-α,IL-1,IL-10,β-EP concentration in plasmaAll the blood samples were centrifuged and collected plasma.These plasma samples were stored in liquid nitrogen at-80 ℃ and prepared for assaying the level of E2,TNF-α,IL-1,IL-10,β-EP.The kit used a double-antibody sandwich enzyme-linked immune-sorbent assay（ELISA）to assay the level of rat E2,TNF-α,IL-1,IL-10,β-EP respectively.Firstly,add rat E2,TNF-α,IL-1,IL-10,β-EP,（samples or standards）to monoclonal antibody enzyme well which is pre-coated with E2,TNF-α,IL-1,IL-10,β-EP monoclonal antibody respectively.Secondly,incubate the samples.Thirdly,after incubation,add rat E2,TNF-α,IL-1,IL-10,β-EP labeled with biotin respectively,and combined with Streptavidin-HRP to form immune complex.Fourthly,after incubation,the unbound conjugate was wash off and added TMB as substrate onto each microplate.TMB was catalyzed by the horse radish peroxidase（HRP）so that the color of the liquid changed into blue.Lastly,at the effect of acid,the color finally becomes yellow.The amount of bound HRP conjugate is reverse proportional to the concentration of E2,TNF-α,IL-1,IL-10,β-EP in the sample respectively.After addition of the substrate solution,the intensity of color developed is reverse proportional to concentration of E2,TNF-α,IL-1,IL-10,β-EP in sample.Run the microplate reader and conduct measurement at 450nm imediately.8.Immunohistochemical method to detect COX-2,PGE2 in the uterine tissuea.Fixation.b.Dehydration and vitrification.c.Waxing,embedding,slicing.d.De-waxing,hydration.e.Antigen retrieval.f.Blocking hydrogen peroxide.g.add non-immune animal serum 50ug,incubation for 10 min at room temperature.h.wash off the serum,incubate tissue with primary antibody 50ug overnight at 4℃.i.Wash with PBS for 3 minutes（3X）.Add secondary antibody labeled with biotin 50ug,then incubate tissue at room temperature for 10 min.Wash with PBS for 3 minutes（3X）.j.Add streptavidin-biotin peroxydase solution 50ug each tissue slide then incubate tissue at room temperature for 10 min.Wash with PBS for 3 minutes（3X）.k.Add fresh prepared DAB solution and observe under a microscope for approximately 3-10 minutes,terminate of color.l.Dehydrate tissue slides consecutively in ethanol for 2 minutes in each solution,mount and photo tissue slides.9.Western-blot method to detect COX-2,PGE2,p-EP in the callosal convolution and prefrontal cortex of brain.a.The brain tissues of rats were stored in cryogenic refrigerator.Brain tissues of each sample weighed 50mg were first broken down mechanically using a blender with nitrogen liquid,and then were removed into EP tube with tissue lysate.With the effect of tissue lysate,protein in brain tissue was extracted.b.The BCA solution was prepared according to the number of samples and to dilute the protein of samples.c.Add the standards and samples into the 96-well strip plate according to instructions and test the concentration by the A562.Calculate out the protein concentration based on the standard curve.d.Proteins were separated by SDS-PAGE（Sodium dodecyl sulfate polyacrylamide gel electrophoresis）and moved from within the gel onto a membrane made of nitrocellulose or polyvinylidene difluoride（PVDF）.PVDF membranes were soaked in the confining liquid overnight at 4℃.e.The primary antibody was added and could bind to an antigen protein.Then a secondary antibody bound to a primary antibody.f.The chromogenic reagent A and B were mixed at a volumetric ratio of 1:1.This mixture was covered the surface of PVDF membranes.The medical X-ray film was directly covered on the PVDF membranes in dark regions for 15 min.At last,photos were developed.10.Statistical analysisThis experiment was complete randomized design.Repetitive measure analysis of variance（ANOVA）was used in analyzing pain threshold.The comparisons in the same group,between groups,interactions and multiple comparisons were performed with LSD test when homogeneity of variance.Dunnett’s T test was used when heterogeneity of variance.P<0.05 were accepted as significant.All data were dealed with SPSS 13.0 statistical software and expressed as the mean ±standard deviation（x±s）.One way ANOVA was applied to analyze the data.The comparisons among groups were performed with LSD test when homogeneity of variance,Dunnett’s T test was used when heterogeneity of variance.P<0.05 were accepted as significant.Results1.Pain threshold in ratsHomogeneity of variance test suggested that the variance is homogeneous（F =1.323,P = 0.112）.The effects of parecoxib on pain threshold in rats were significantly different between groups（F = 10.090,P<0.01）.In the same group,there were significant differences in four different levels of the factors（F = 27.854,P<0.01）.Interactions were found between pain threshold and treatment factors（F=8.277,P<0.01）.Compared with group C,group M and group A were found significant differences（P<0.01）.However,group B was no significant differences compared with group C.Compared with group M,group B（P=0.002）was found significant differences but group A（P=0.534）.Compared with group A,group B was found significant differences（P=0.011）.2.The number of writhes in ratsHomogeneity of variance test suggested that the variance is heterogeneous（F=16.491,P<0.01）.The number of writhes in rats was significantly different between groups（F=90.379,P<0.01）.Compared with group C,group M and group A were found significantly writhing more（P<0.01）.However,group B was no significant differences compared with group C（P=0.067）.Compared with group M,group B were found significantly writhing less（P<0.01）,but group A was no significant differences.Compared with group A,group B were found significantly writhing less（P<0.01）.3.Concentration of E2 in rat plasmaHomogeneity of variance test suggested that the variance is homogeneous（F=1.424,P=0.249）.Concentration level of E2 in rat plasma was significantly different between groups（F=3.117,P=0.036）.Compared with group C,concentration of E2 in group M,A and B were found significantly higher（P<0.05）.Compared with group M,there were no significant differences from group A or group B（P=0.858,P=0.892）.4.COX-2 expression of endometrium in ratsHomogeneity of variance test suggested that the variance is heterogeneous（F=9.971,P<0.01）.COX-2 expression of endometrium in rats was significantly different between groups（F=86.744,P<0.01）.Compared with group C,COX-2 expression of endometrium in group M,A and B were found significantly higher（P<0.01）.Compared with group M,both group A and group B expressed COX-2 on lower level,from which was significant different（P<0.05）.There were significant differences between group A and group B（P<0.05）.5.PGE2 expression of endometrium in ratsHomogeneity of variance test suggested that the variance is heterogeneous（F=4.268,P=0.01）.PGE2 expression of endometrium in rats was significantly different between groups（F=82.519,P<0,01）.Compared with group C,PGE2 expression of endometrium in group M,A and B were found significantly higher（P<0.01）.Compared with group M,PGE2 expression on lower level in group A was not significant different（P=0.071）,however,there were no significant differences in group B.There were significant lower in group B compared with group A（P<0.05）.6.Concentration of TNF-a in rat plasmaHomogeneity of variance test suggested that the variance is heterogeneous（F=8.965,P<0.01）.Concentration of TNF-a in rat plasma was significantly different between groups（F=21.038,P<0.01）.Compared with group C,Concentration of TNF-a in group M,A and B were found to increase significantly（P<0.01）.Compared with group M,Concentration of TNF-a in both group A and group B decreased significantly which had statistical significance（P<0.05）.However,there were no significant differences between group A and group B（P=0.932）.7.Concentration of IL-1 in rat plasmaHomogeneity of variance test suggested that the variance is heterogeneous（F=7.601,P<0.01）.Concentration of IL-1 in rat plasma was significantly different between groups（F=29.345,P<0.01）.Compared with group C,Concentration of IL-1 in group M,A and B were found to increase significantly（P<0.05）.Compared with group M,Concentration of IL-1 in both group A and group B decreased significantly which had statistical significance（P<0.05）.And there were significant differences between group A and group B（P<0.05）.8.Concentration of IL-6 in rat plasmaHomogeneity of variance test suggested that the variance is heterogeneous（F=3.011,P=0.04）.Concentration of IL-6 in rat plasma was significantly different between groups（F=14.767,P<0.01）.Compared with group C,Concentration of IL-6 in group M,A and B were found to increase significantly（P<0.05）.Compared with group M,Concentration of IL-6 in both group A and group B decreased significantly which had statistical significance（P<0.05）.However,there were no significant differences between group A and group B（P=0.999）.9.Concentration of β-EP in rat plasmaHomogeneity of variance test suggested that the variance is homogeneous（F=2.088,P=0.116）.Concentration of β-EP in rat plasma did not differ significantly between groups（F=2.711,P=0.056）.Compared with group C,Concentration of IL-6 in group M was significantly lower（P<0.05）,however,neither did group A nor group B have statistical significance（F=0.283,P=0.911）.Compared with group M,group B（P<0.05）was found significant higher but group A（P=0.20）.There were no significant differences between group A and group B（P=0.237）.The results were shown in Table3-4 and Figure3-4.10.Expression of COX-2 in rat callosal convolutionHomogeneity of variance test suggested that the variance is homogeneous（F=0.202,P=0.892）.COX-2 expression of callosal convolution in rats was significantly different between groups（F=41.486,P<0.01）.Compared with group C,COX-2 expression of callosal convolution in group M,A and B were found significantly increasing（P<0.01）.Compared with group M,both group A and group B expressed COX-2 on lower level,from which was significant different（P<0.05,P<0.01）.There were no significant differences between group A and group B（P=0.068）.11.Expression of COX-2 in rat hippocampHomogeneity of variance test suggested that the variance is homogeneous（F=0.564,P=0.654）.COX-2 expression in rat hippocamp was significantly different between groups（F=195.048,P<0.01）.Compared with group C,COX-2 expression in hippocmp in group M,A and B were found significantly increasing（P<0.01）.Compared with group M,both group A and group B expressed COX-2 on lower level,from which was significant different（P<0.05）.There were no significant differences between group A and group B（P=0.864）.12.Expression of COX-2 in prefrontal cortex of brainHomogeneity of variance test suggested that the variance is homogeneous（F=2.118,P=0.176）.COX-2 expression of prefrontal cortex of brain was significantly different between groups（F=50.369,P<0.01）.Compared with group C,COX-2 expression of prefrontal cortex of brain in group M,A and B were found significantly increasing（P<0.01）.Compared with group M,both group A and group B expressed COX-2 on lower level,from which was significant different（P<0.05,P<0.01）.COX-2 expression in group A was significantly higher than that of group B（P<0.05）.13.Expression of COX-2 in spinal cordHomogeneity of variance test suggested that the variance is homogeneous（F=3.846,P=0.057）.COX-2 expression in spinal cord was significantly different between groups（F=195.048,P<0.01）.Compared with group C,COX-2 expression in spinal cord in group M,A and B were found significantly increasing（P<0.01）.Compared with group M,both group A and group B expressed COX-2 on lower level,from which was significant different（P<0.05,P<0.01）.There were significant differences between group A and group B（P<0.05）.14.Expression of PGE2 in rat callosal convolutionHomogeneity of variance test suggested that the variance is heterogeneous（F=90.281,P<0.01）.PGE2 expression of callosal convolution in rats was significantly different between groups（F=90.281,P<0.01）.Compared with group C,PGE2 expression of callosal convolution in group M,A and B were found significantly increasing（P<0.01,P<0.05）.Compared with group M,both group A and group B expressed COX-2 on lower level,from which was significant different（P<0.05）.There were no significant differences between group A and group B（P=0.872）.15.Expression of PGE2 in rat hippocampHomogeneity of variance test suggested that the variance is homogeneous（F=3.45,P=0.072）.PGE2 expression in rat hippocamp was significantly different between groups（F=38.274,P<0.01）.Compared with group C,PGE2 expression in hippocamp in group M,A and B were found significantly increasing（P<0.01）.Compared with group M,both group A and group B expressed PGE2 on lower level,from which was significant different（P<0.05,P<0.01）.There were no significant differences between group A and group B（P=0.06）.16.Expression of PGE2 in prefrontal cortex of brainHomogeneity of variance test suggested that the variance is homogeneous（F=0.161,P=0.920）.PGE2 expression in prefrontal cortex of brain was significantly different between groups（F=218.544,P<0.01）.Compared with group C,PGE2 expression in prefrontal cortex of brain in group M,A and B were found significantly increasing（P<0.01）.Compared with group M,both group A and group B expressed PGE2 on lower level,from which was significant different（P<0.05,P<0.01）.There were no significant differences between group A and group B（P<0.05）.17.Expression of PGE2 in spinal cordHomogeneity of variance test suggested that the variance is homogeneous（F=4.456,P=0.04）.PGE2 expression in spinal cord was significantly different between groups（F=65.719,P<0.01）.Compared with group C,PGE2 expression in spinal cord in group M,A and B were found significantly increasing（P<0.05）.Compared with group M,group B expressed PGE2 on significantly lower level（P<0.05）,however,group A（P=0.152）did not significantly differ from group M.There were no significant differences between group A and group B（P=0.219）.18.Expression of β-EP in callosal convolutionHomogeneity of variance test suggested that the variance is homogeneous（F=2.862,P=0.104）.β-EP expression in callosal convolution was significantly different between groups（F=59.638,P<0.01）.Compared with group C,β-EP expression in callosal convolution in group M,A and B were found significantly decreasing（P<0.01,P<0.01,P<0.05）.Compared with group M,both group A and group B expressed β-EP were significantly increasing（P<0.05）.Compared with group A,β-EP expression in group B increased significantly（P<0.05）19.Expression of β-EP in rat hippocampHomogeneity of variance test suggested that the variance is homogeneous（F=3.567,P=0.067）.β-EP expression in hippocamp was significantly different between groups（F=53.121,P<0.01）.Compared with group C,β-EP expression in hippocamp in group M,A and B were found significantly decreasing（P<0.01,P<0.01,P<0.05）.Compared with group M,both group A and group B expressed β-EP were significantly increasing（P<0.01）.Compared with group A,β-EP expression in group B increased significantly（P<0.05）.20.Expression of β-EP in prefrontal cortex of brainHomogeneity of variance test suggested that the variance is homogeneous（F=2.523,P=0.131）.β-EP expression in prefrontal cortex of brain was significantly different between groups（F=24.707,P<0.01）.Compared with group C,β-EP expression in prefrontal cortex of brain in group M,A and B were found significantly decreasing（P<0.01,P<0.01,P<0.05）.Compared with group M,both group A and group B expressed β-EP were significantly increasing（P<0.05,P<0.01）.Compared with group A,β-EP expression in group B increased significantly（P<0.05）.21.Expression of β-EP in spinal cordHomogeneity of variance test suggested that the variance is homogeneous（F=1.809,P=0.224）.β-EP expression in prefrontal cortex of brain was significantly different between groups（F=23.263,P<0.01）.Compared with group G,β-EP expression in prefrontal cortex of brain in group M,A and B were found significantly decreasing（P<0.01,P<0.01,P<0.05）.Compared with group M,both group A and group B expressed β-EP were significantly increasing（P<0.05,P<0.01）.There were no significant differences between group A and group B（P=0.067）.Conclusions1.The establishment of primary dysmenorrheal rat model is successful.2.Pain threshold of primary dysmenorrheal rat model decreases.3.The use of parecoxib increases pain threshold of primary dysmenorrheal rat model4.The use of parecoxib decreases COX-2 and PGE2 expression of endometrium in primary dysmenorrheal rat model.5.The use of parecoxib decreases the concentration of TNF-α,IL-1,IL-6 but increases the concentration of β-EP in rat plasma.6.The use of parecoxib decreases COX-2 and PGE2 expression in callosal convolution,prefrontal cortex,hippocamp and spinal cord,but increases β-EP expression in callosal convolution of brain,prefrontal cortex,hippocamp and spinal cord. |
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