The Machinism Of Endothelin And Receports In Pain Conduction In Ovarian Cancer

Background: there are about 10 million new patients with neoplasms every year in the survey of the world health organization(WHO), and 30%- 50% of patients advanced on diagnosis with moderate and severe pain.70% patients with ovarian cancer is in the late diagnosis because of it,s hidden. With improvement of diagnosis and therapy,living time prolonged,75%-95% patients endure cancer pain. Pain is one of the serious symptoms which affect the life quality of patients with ovarian cancer.Cancer pain is one of emphasis of cancer therapy.The study recent years on the pathophysiology of neural invasive cancer pain and pain signal transduction mechanisms has showed that the ion channels and receptors in the pain signal transduction can be a new therapeutic targets.The research has found out that the endothelin has been a new cancer treatment targets.There are endothelin A receptor and endothelin B receptor in mammals. The literature has suggested that endothelin receptor antagonist can reduce tumor pain,but the mechanism is still not clearly defined.The latest research has showed that the endothelin-1 can induce a fall of thermal threshold via the phosphorylation sites Ser-800 on transient receptor potential vanilloid subtype-1(TRPV1),which may trigger cascaded effects in the sensory neurons that result in heat hyperalgesia. Besides, mitogen-activated protein kinases(MAPKs) is a class of serine/threonine protein kinases in eukaryotic cells. p38 MAPK signal transduction pathway was one of the multiple parallel MAPK signal transductionpathways, involving in the formation and maintenance of pain.The research has found out that the phosphorylated p38MAPK(p-p38MAPK) in the dorsal root ganglion can increase TRPV1 expression,and transportation to the damaging sensory neurons,which is closely related to the painfui degree.This study aims to further investigate whether the endothelin enhance endothelin receptor and involve the pain regulation of ovarian cancer by Protein Kinase C.Objective:1 To explore the change of cancer pain in the orthotopic implantation model of ovarian cancer in mice with injection of endothelin receptor agonists(ET) and endothelin receptor antagonist(BQ788、BQ123).2 To investigate the expression of ETR、ETBR、ETAR in the dorsal root ganglia of the orthotopic implantation model of ovarian cancer in mice,and explore the relationship with ovarian cancer pain.3 To investigate the expression of p38MAPK、p-p38 MAPK in the dorsal root ganglia of the orthotopic implantation model of ovarian cancer in mice,and explore the relationship with endothelin receptor.Method:1 Five week female BALB-C mices were randomly divided into 5 groups: Blank control group,Model control group,Model A group injection with ET-1,Model B group injection with endothelin A receptor antagonist(BQ123) and Model C group injection with endothelin B receptor antagonist(BQ788).To establish the orthotopic implantation model of ovarian cancer in mice.2 To explore the neuropathic pain behaviors in model mice through measure the thermal withdrawal latency and mechanical withdrawal threshold of the mices.3 Immunohistochemistry were immunostained to detect the expression of ETAR、ETBR、ETR、p38MAPK、p-p38 MAPK in the dorsal root anglia of the orthotopic implantation model of ovarian cancer in mice.Result:Neuropathic pain behaviors showed that:1 The thermal withdrawal latency and mechanical withdrawal threshold in the model control group mices were lower than the blank control group.the ovarian cancer pain is relation with the formation of tumor.2 Control with the model control group: No change in the thermal withdrawal latency and mechanical withdrawal threshold was observed in the model A group; The thermal withdrawal latency and mechanical withdrawal threshold were higher in the model B group and the model C group.It showed that endothelin is very close relation to ovarian cancer pain.3 The thermal withdrawal latency and mechanical withdrawal threshold in the model A group mices were lower than the model B group and the model B group; The thermal withdrawal latency and mechanical withdrawal threshold in the model C group mices were higher than the model B group.The immunohistochemistry result showed that:1 In dorsal root ganglia, the model control group,s ETR expression was higher than the blank control group.The model A group had more ETR than the model control group.It is very close relation to ovarian cancer pain.2 The model control group,s ETBR expression was higher than the ETAR expression; The model B group,s ETAR expression was higher than the model C group; The model C group,s ETBR expression was higher than the model B group.This showed that the differences expression within the ETAR and ETBR was relation to ovarian cancer pain.3 The model control group had more p38 MAPK and p-p38 MAPK than the blank control group; The model A group,s p-p38 MAPK expression was higher than the model B group and the model C group; The model C group,s p-p38 MAPK expression was lower than the model B group.Conclusion:1 The endothelin and endothelin receptor involves in the formation of ovarian cancer pain.2 P38-MAPK participates in the ovarian cancer pain which is related to the endothlin.