Effects Of ErbB4 Receptors In The Dorsal Horn On Electroacupuncture Treatment Of CFA Pain In Mice

ObjectiveWe found that ErbB4 receptor was abundantly expressed in layer I and II of spinal dorsal horn,and the effect of EA analgesia was significant in clinic,but the mechanism of acupuncture analgesia was not completely clear.Therefore,we studied the effect of ErbB4 receptor in spinal dorsal horn on chronic inflammatory pain mice treated with complete Freund’ s adjuvant(CFA)by electroacupuncture.To observe the changes of behavior and NRG1-ErbB4 expression in CFA mice with chronic inflammatory pain during electroacupuncture.Method(1)Firstly,using CFA pain model mice,Von Frey and Hargreaves pain behavior were used to test the changes of Paw Withdrawal Threshold(PWT)and Thermal Withdrawal Latencies(TWL)of CFA model mice during electroacupuncture,respectively,to explore the effects of electroacupuncture at different frequencies on CFA pain model mice.(2)The effect of electroacupuncture intervention on the level of NRG1 in spinal dorsal horn and dorsal root ganglion(DRG)in mice with inflammation and pain of CFA was measured by Elisa.(3)The expression of ErbB4 neurons in spinal cord and dorsal root ganglion(DRG)was measured by immunofluorescence;(4)The CFA model mice were injected by intrathecal administration of NRGl and intrathecal injection of EGFR inhibitor AG1478,respectively,to investigate the therapeutic effect of electroacupuncture analgesia.(5)The chronic inflammation model of CFA was established by conditional knockout PV-ErbB4-/-mice with specific ErbB4 knockout on Palvalbumin(PV)neurons,and the role of ErbB4 expression on PV-positive neurons in electroacupuncture analgesia was observed.Results(1)Electroacupuncture of Zusanli and Sanyinjiao at different frequencies can improve mechanical pain and hyperalgesia in mice with chronic inflammatory pain of CFA,but the 2 Hz electroacupuncture has the best therapeutic effect.(2)Elisa results showed that there was no change in NRG1 in spinal dorsal horn and the content of DRG decreased in CFA model mice compared with the normal group,while the expression of NRG1 in spinal dorsal horn and DRG increased after electroacupuncture compared with the model group.(3)ErbB4 receptor was not distributed in DRG,but was highly expressed in the lamina I and II layers of spinal dorsal horn,including PV positive interneurons.(4)Intrathecal injection of EGFR inhibitor AG1478 could partially inhibit the therapeutic effect of EA analgesia.Intrathecal injection of NRG1 can improve the mechanical pain and hyperalgesia of chronic inflammation pain in CFA,but the combination of exogenous NRG1 and electroacupuncture can not further enhance the analgesic effect of chronic inflammation pain in CFA mice.(5)Compared with the control group,PV-ErbB4-/-mice after electroacupuncture had lower PWT and no change in TWL.ConclusionElectroacupuncture Zusanli and Sanyinjiao can improve the mechanical pain and thermal hyperalgesia of CFA chronic inflammatory pain model mice.Electroacupuncture can increase the expression of NRG1 in spinal dorsal horn and DRG.ErbB4 receptor in spinal dorsal horn may participate in the analgesic effect of electroacupuncture.