Study On The Chronic Pain Characteristics Of Alzheimer’s Disease And Possible Mechanism Of Electroacupuncture Therapy

Objective:In order to verify if the aging process and AD pathology affect the chronic pain modulation or not,we investigated this issue and explorated the analgesic effect of electroacupuncture(EA)at ST36 by animal studies.Methods:The 5×FAD transgenic and wild type mice at 3-,6-and 9-month-old were studied.complete Freund’s adjuvant(CFA)was injected into the pelma when the pain threshold of mouse is relatively stable,then we assessed the variation of withdrawal percentage in the following 5 days.The emotional response was collected by open field test and elevated plus maze in inflammatory conditions.Finally,we compared the gait patterns between two group by quantitative gait analysis systems.Multi-channel in vivo recording technique is a useful tool in the research of neuronal activity and local field potential.To find potential concordance between von Frey sitimulated neuronal reaction and withdrawal response,we contrasted the neuronal firing initiation and peak z-score value between 5×FAD group and WT group.To preclude the reduction of excitatory neurons,we identified the proporrion of Aβ plaque area and glutamatergic neurons between the two groups of different ages.Subsequent Golgi staining made the comparison of dendritic complexity,spine density and mature spine proportion possible.By virtue of viral-mediated gene transfection,we managed to excited the pyramidal neurons of 5×FAD mice by Ch R2 expression and inhibited them in WT mice by h M4 D expression.Then we tried to modulate the withdrawal response of von Frey test 4 hr after CFA injection by neuronal activity manipulation.Then,intracerebroventricular injection of Rac-1 inhibitor NSC23766 was performed 3days prior to CFA injection.To further testify if the alterations of dendritic spine in5×FAD mice take a part in pain modulation,we conducted the Golgi staining,neuronal activity analysis and behavioral experiment.Finally,electroacupuncture on ST36 was applied.The neuronal activity analysis was conduct synchronously with von Frey test.Result:1.The 5×FAD mice at 6-and 9-months-old performed a higher mechanical pain threshold than the control group.2.Alzheimer’s disease pathalogy impaires the bidirectional regulation of central sensitizion and the anterior cingulate cortex pyramidal neuronal activity.3.The spine density,proportion of mature spine and dendritic complexity generally reduced in 6-month-old 5×FAD group.The administration of NSC23766 could mimic the analgesia effect that similar to 5×FAD mice.4.Electroacupunture ST36 point has the function of reliefing imflamatory persistent pain by inhibiting the activity of glutamatergic neurons in ACC.Conclusion:In summary,AD performs a deficient in dendritic spine density which may cause the impairement of chronic pain central sensitization.Electroacupuncture in ST36 help ease the inflammatory pain by reducing the ACC neuronal activity.