Expression Of 5-HT And 5-HT2A Receptor MRNA And BDNFmRNA In Hippocampus Of Rats With Inflammatory Pain And The Effect Of Duloxetine In Bolcking It

Objective:The unpleasant emotions caused by pain can affect the perception of the pain.Hippocampus which an important part of the limbic system,is involved in processing and adjusting pain stimulation,especially the emotional-motivation part of the pain.The change of the morphological plasticity and the nerve chemicals of hippocampus is related with the pain closely,but the mechanism is not fully clear.Serotonin(5-hydroxytryptamine,5-HT)and 5-HT2 A receptor are involved in the mediation of the pain.Brain derived neurotrophic factor(BDNF)is able to adjust the plasticity of neurons in hippocampus.Therefore,the purpose of this experiment is:(1)To explore changes of pain threshold and depression-like behavior and the expression of 5-HT and 5-HT2 A receptor mRNA and BDNFmRNA of hippocampus in inflammatory pain rat;(2)To explore the impact of duloxetine on pain threshold and depression-like behavior and the expression of 5-HT and 5-HT2 A receptor mRNA and BDNFmRNA of hippocampus in inflammatory pain rat.(3)The ralationship between 5-HT and BDNF.Methods:72 adult male SD rats were randomly divided into the control group and the experiment group:inflammatory pain modelgroup;inflammatory pain model+saline by intragastile administration group and inflammatory pain model+duloxetine by intragastile administration group,18 rats in each group.The inflammatory pain models were established by subcutaneously injecting mixture of CFA and saline into the left plantar of the rats.Fluoxetine(10mg/(kg.d))were delivered to rats by intragastile administration for 2 weeks.The same dose of saline for about 2 weeks by intragastile administration.The alterations of 50%paw withdrawal threshold(PWT)were measured at 2 weeks later and before CFA injection with Von Frey Fibres.The depression-like behaviors tested with sucrose preference test.The level of 5-HT2 A receptor mRNA and BDNF mRNA in the hippocampus was detected by RT-PCR and the expression of 5-HT in the hippocampus was detected by ELISA.Results:Before treatment,the difference among 50%PWT of the four groups had no statistical significance.Compared with the control group,50%PWT and sugar consumption rate of inflammatory pain model group is decreased,and the difference had statistically significant(P<0.05).Compared with the inflammatory pain model+saline by intragastile administrationthe group,the 50%PWT(P<0.01)and sugar consumption rate(P<0.05)was higher in the inflammatory pain model+duloxetine by intragastile administration group.The inflammatory pain model group compared with the control group,5-HT in hippocampus decreased(P<0.05),the expression of 5-HT2 A receptor mRNA in thehippocampus is lower,but the difference was not statistically significant(P>0.05),the expression of BDNFmRNA is lower(P<0.05).Compared with inflammatory pain+saline by intragastile administrationthe group,in inflammatory pain+duloxetine by intragastile administrationthe group the5-HT in hippocampus was increased(P<0.01),the expression of 5-HT2 A receptor mRNA and BDNFmRNA in hippocampus was higher(P<0.05).Conclusion:The expression of 5-HT and 5-HT2 A receptor mRNA and BDNFmRNA in hippocampus is decreased in the rat with chronic inflammatory pain and the pain threshold is decreased and depression-like behavioral appears;Duloxetine can improve pain threshold,improve depression of the rat with chronic inflammatory pain,and increasing of 5-HT and 5-HT2 A receptor mRNA expression and the BDNFmRNA expression in hippocampus may participate in this mechanism;5-HT may regulation BDNF.Though its 2A receptor.