Abstract: Objective: To observe the effect of inhibition or activation of astrocytes in primary somatosensory cortex on analgesia effect of electroacupuncture on inflammatory pain and explore the potential mechanism of electroacupuncture analgesia. Methods: Experiment 1, 32 male C57 mice were randomly divided into 4 groups: sham- CFA group, CFA group, CFA + sham- EA group and CFA + EA group,with 8 mice in each group. A model of inflammatory pain was established by subcutaneous injection of Complete Freund's Adjuvant (CFA) into the left posterior pelma. After the establishment of the model, electrical acupuncture was performed on the mice in CFA + EA group at “Huantiao (GB30)” and “Yanglingquan (GB34)”points on the left leg for 7 consecutive days, 30 minutes each time, with the parameter of 2 Hz and 1 mA. The paw withdrawal threshold (PWT) and the thermal latency (TL) were detected one day before and one day after modeling and on the day 1, 3, 5, 7 of electroacupuncture treatment. Experiment 2, 32 male C57 mice were randomly divided into 4 groups: CFA + aCSF group, CFA+L-α-AAA group,CFA+aCSF+EA group and CFA+L-α-AAA+EA group,with 8 mice in each group. All mice underwent CFA modeling. After modeling,CFA+L-α-AAA group and CFA+L-α-AAA+EA group were injected with L- α-aminoadipic acid (an astrocyte-selective gliotoxin) to achieve specific inhibition of astrocytes in the hindlimb region of the right primary somatosensory cortex (S1HL),while CFA+aCSF group and CFA+aCSF+EA group were injected with artificial cerebrospinal fluid. Three days after brain injection, the CFA+aCSF+EA group and CFA+L-α-AAA+EA group were given electroacupuncture therapy,with the protocol of experiment 1. PWT and TL were detected one day before and one day after modeling and on the day 1,3,5,7 of electroacupuncture treatment. Experiment 3,16 male C57 mice were randomly divided into two groups: CFA + EA + CNO group (chemogenetic activation group) and CFA + EA + saline group (chemogenetic control group), with 8 mice in each group. Mice in both groups were injected with recombinant adeno- associated virus in the right S1HL region, and 3 weeks later, CFA modeling was performed. Electroacupuncture treatment was performed followed the protocol of experiment 1. The CFA+ EA + CNO group was intraperitoneally injected with Clozapine N- oxide (CNO) 40 minutes before electroacupuncture,while the CFA + EA + saline group was intraperitoneally injected with equal volume of normal saline. PWT and TL were detected one day before and one day after modeling and on the day 1,3, 5, 7 of electroacupuncture treatment. Results: Experiment 1, 24 hours after modeling, PWT and TL were significantly decreased in all groups except sham- CFA group (P<0.05), indicating that model had been successfully established. Compared with CFA group, the PWT of CFA + EA group was significantly increased on the third,fifth and seventh day after electroacupuncture treatment (P<0.05) and the TL was significantly increased on the third, fifth and seventh day of electroacupuncture treatment (P<0.05). Experiment 2,compared with CFA+aCSF group,PWT and TL were significantly increased in CFA+L- α- AAA group (P<0.05),and last from the day 1 to the day 7 of electroacupuncture. On the fifth and seventh day of electroacupuncture,there were no significant differences in PWT and TL between CFA+L-α-AAA+ EA group and CFA+EA group (P>0.05). On the d day 7 of electroacupuncture,compared with CFA+L-α- AAA group,PWT and TL were significantly increased in CFA+L-α-AAA+EA group (P<0.05). Experiment 3, compared with the pain threshold after modeling, the PWT and TL of CFA + EA + saline group were significantly increased at the day 3,5,7 of electroacupuncture (P<0.05). Compared with CFA+EA+saline group, the PWT and TL of CFA + EA + CNO group were significantly decreased at the day 3, 5, 7 of electroacupuncture (P<0.05). Conclusion: Electroacupuncture can effectively relieve CFA- induced inflammatory pain, inhibition of astrocytes in primary somatosensory cortex can simulate the analgesia effect of electroacupuncture,while chemogenetic activation of astrocytes in primary somatosensory cortex can reverse the analgesic effect of electroacupuncture, suggesting that primary somatosensory cortex astrocytes are involved in the treatment of inflammatory pain by electroacupuncture.