| BackgroundDepression is a common mental disorder and often accompanied with unexplained painful physical symptoms.A large number of clinical data show that depression and pain share a high degree of comorbidity.Chronic pain combined depression are frequently encountered clinically.Chronic pain and depression share a complex,reciprocal relationship.Pain adversely affects the prognosis and treatment of depression and vice versa.Improvement in pain correlates with improvement in depression.Effective treatment of pain symptoms has been shown to improve the remission rate of patients with depression.In a word,when chronic pain and depression occur concomitantly,the prognosis is worse than in either case,leading to greater functional impairment,longer duration,and less effective medication.Therefore,depression combined pain brings a great burden to individuals and society.Pain and depression have common pathogenesis,which is very important to promote the occurrence and development of depression and chronic pain.Inflammatory mechanisms plays an important role in the pathogenesis of depression combined pain.A large number of literatures have shown that depression combined pain is related to the elevated serum/plasma proinflammatory cytokines(including Interleukin IL-1,IL-6 and tumor necrosis factor alpha(TNF-?)),and depression combined pain up-regulated the expression of proinflammatory cytokines in the brain.Acupuncture as a simple,effective,safe and non-invasive treatment,previous studies have shown that acupuncture has a significant effect on depression and chronic pain.There is evidence that electroacupuncture at Zusanli and transcutaneous auricular vagus nerve stimulation(taVNS)through cholinergic anti-inflammatory pathway to achieve anti-inflammatory effects.In this study,Chronic unpredictable mild stimulation(CUMS)combined Chronic constriction injury of the sciatic nerve(CCI)model was selected.taVNS and electroacupuncture at Zusanli(ST 36)were used as intervention methods.The success of the model and the changes of curative effect before and after intervention were evaluated by observing the body weight,sucrose consumption,crossing and rearing for open field test,mechanical withdrawl threshold and thermal stimulation latency.The concentration changes of plasma TNF-? and substance P were detected in model rats after taVNS and electroacupuncture at ST 36 intervention.The expression of TNF-? in prefrontal cortex(PFC),hippocampus,hypothalamus and amygdala were detected after taVNS and electroacupuncture at ST 36 intervention.To explore the cholinergic anti-inflammatory mechanism of acupuncture on depression combined chronic somatic pain in rats.ObjectiveTo explore the cholinergic anti-inflammatory mechanisms of taVNS and electroacupuncture at ST 36 on depression combined chronic somatic pain in rats.MethodsForty healthy male SD rats were randomly divided into control,model,taVNS and electroacupuncture at ST 36 group,with 10 rats in each group.In addition to the control group,the other three groups of rats were single cage rearing.CUMS combined CCI were used to make depression combined chronic somatic pain model in three other groups.CCI was performed 28 days after CUMS modeling.The success of the model was observed by the sucrose consumption,mechanical withdrawl threshold and thermal stimulation latency.After the modeling is completed,intervention is carried out.In the taVNS group,HANS-100A instrument was connected with a positive and negative electrode self-adsorption conductive magnet which was non-invasively fixed in the bilateral cavity of auricular concha of rats.The electroacupuncture was inserted perpendicularly into the skin 5 mm apart at bilateral ST 36 in ST 36 group.ST 36 locates 5 mm below the humeral head.taVNS group and ST 36 group were interfered for 28 consecutive days.The intensity and frequency of electrical stimulation were set at 2 mA and 15 Hz.Waveform was selected as disperse-dense wave.Weight,crossing for open field test,rearing for open field test,mechanical withdrawl threshold and thermal stimulation latency in each group were measured every two weeks from 28 days before modeling.The sucrose consumption in each group was measured 28 days before modeling,0 day after modeling and 28 days of intervention.To observe the effect of taVNS and electroacupuncture at ST 36 on depression and pain-like behavior in CUMS combined CCI model rats.At 24 day of intervention,the changes of plasma TNF-? and substance P concentration in taVNS group and ST 36 group were detected by ELISA method before electroacupuncture,electroacupuncture at 15 minutes and electroacupuncture at 30 minutes.At 28 days of intervention,the concentration of TNF-a and substance P in plasma of the four groups were detected by ELISA,and the expression of TNF-a in PFC,hippocampus,hypothalamus and amygdala of the four groups was detected by Western blot.Results(1)Weight:Compared with the control group,the weight decreased significantly in model,taVNS and ST 36 group at 14 days before modeling and 0 day after modeling(P<0.001,P<0.01).The weight decreased significantly in taVNS and ST 36 group at 14 days after intervention(P<0.05).The weight decreased significantly in taVNS group at 28 days of intervention(P<0.05).Compared with the model group,the weight decreased significantly in taVNS group at 28 day of intervention(P<0.05).Compared with ST 36 group,the weight decreased in taVNS group,but there was no statistical difference(P>0.05).(2)Sucrose preference test:Compared with the control group,the sucrose consumption decreased significantly in the model,taVNS and ST 36 group at 0 day after modeling(P<0.05).Compared with the model group,the sucrose consumption increased significantly in the taVNS group at 28 days of intervention(P<0.05).The sucrose consumption increased in the ST 36 group at 28 days of intervention,but there was no statistical difference(P>0.05).Compared with the ST 36 group,the sucrose consumption increased in the taVNS group at 28 days of intervention,but there was no statistical difference(P>0.05).(3)Open field test:Compared with the control group,the crossing for open field test decreased significantly in taVNS and ST 36 group at 14 days before modeling(P<0.05).The crossing for open field test decreased significantly in model,taVNS and ST 36 group at 0 day after modeling(P<0.01).Compared with the control group,the rearing for open field test decreased significantly in ST 36 group at 14 days before modeling(P<0.05).The rearing for open field test decreased significantly in model and ST 36 group at 0 day after modeling(P<0.05).The rearing for open field test decreased significantly in taVNS group at 28 days of intervention(P<0.05).Compared with the ST 36 group,the crossing and rearing for open field test decreased in taVNS group at 28 days of intervention,but there was no statistical difference(P>0.05).(4)Mechanical withdrawl threshold:Compared with the control group,the mechanical withdrawl threshold decreased significantly in the model,taVNS and ST 36 group at 0 day after modeling(P<0.001).Compared with the model group,the mechanical withdrawl threshold increased in the ST 36 and taVNS group at 28 days of intervention,but there was no statistical difference(P>0.05).Compared with the taVNS group,the mechanical withdrawl threshold increased in the ST 36 group at 28 days of intervention,but there was no statistical difference(P>0.05).(5)Thermal stimulation latency:Compared with the control group,the thermal stimulation latency decreased significantly in the model,taVNS and ST 36 group at 0 day after modeling(P<0.01,P<0.05).Compared with the control group,the thermal stimulation latency decreased significantly in the model group at 28 days of intervention(P<0.01).Compared with the model group,the thermal stimulation latency increased significantly in the ST 36 and taVNS group at 28 days of intervention(P<0.05).Compared with the taVNS group,the thermal stimulation latency increased in the ST 36 group at 28 days of intervention,but there was no statistical difference(P>0.05).(6)Concentration of TNF-a and substance P in Plasma:Compared with that at 0 min,the concentration of TNF-a in plasma decreased in the taVNS and ST 36 group at 15 mins and 30 mins,but there was no statistical difference(P>0.05).Compared with the control group,the concentration of TNF-a in plasma increased significantly in model group at 28 days of intervention(P<0.05).Compared with the model group,the concentration of TNF-a in plasma decreased significantly in ST 36 group at 28 days of intervention(P<0.01).The concentration of TNF-a in plasma decreased in taVNS group at 28 days of intervention,but there was no statistical difference(P>0.05).Compared with the taVNS group,the concentration of TNF-a in plasma decreased in ST 36 group at 28 days of intervention,but there was no statistical difference(P>0.05).Compared with that at 0 min,the concentration of substance P in plasma decreased in the taVNS group at 15 mins and 30 mins,but there was no statistical difference(P>0.05).Compared with that at 0 min,the concentration of substance P in plasma decreased in the ST 36 group at 15 mins,but there was no statistical difference(P>0.05).Compared with the control group,the concentration of substance P in plasma decreased in the model group at 28 days of intervention,but there was no statistical difference(P>0.05).Compared with the model group,the concentration of substance P in plasma increased in the ST 36 group at 28 days of intervention,but there was no statistical difference(P>0.05).Compared with the taVNS group,the concentration of substance P in plasma increased in the ST 36 group at 28 days of intervention,but there was no statistical difference(P>0.05).(7)The expression of TNF-a in PFC,hippocampus,hypothalamus and amygdala:At 28 days of intervention,compared with the control group,the expression level of TNF-a in the hippocampus,hypothalamus and amygdala increased significantly in the model group(P<0.05).The expression level of TNF-a in the PFC increased in the model group(P=0.058).Compared with the model group,the expression level of TNF-a in the amygdala decreased significantly in the ST 36 group(P<0.05).The expression level of TNF-a in the hippocampus and hypothalamus decreased in the taVNS group(P=0.054,P=0.052).The expression level of TNF-a in the PFC and amygdala decreased in taVNS group,but there was no statistical difference(P>0.05).The expression level of TNF-a in the PFC,hippocampus and hypothalamus decreased in the ST 36 group,but there was no statistical difference(P>0.05).Compared with the taVNS group,the expression level of TNF-a in the PFC and amygdala decreased in the ST 36 group,but there was no statistical difference(P>0.05).Compared with the ST 36 group,the expression level of TNF-a in the hippocampus and hypothalamus decreased in the taVNS group,but there was no statistical difference(P>0.05).Conclusion(1)CUMS combined CCI can induce depression combined chronic somatic pain-like behavior under solitary care for 28 consecutive days.(2)After 28 consecutive days of intervention,taVNS and electroacupuncture at ST 36 could improve depression combined chronic somatic pain-like behavior.(3)Compared with the control group,the levels of TNF-a in plasma,PFC,hippocampus,hypothalamus and amygdala increased in rats with depression combined chronic somatic pain,and the expression of TNF-a was down-regulated by taVNS and electroacupuncture at ST 36. |
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