Electroacupuncture alleviates chronic migraine hyperalgesia by suppressing microglial P2X4R-BDNF signaling in the trigeminal nucleus caudalis

Abstract

: Objective To observe the effect of electroacupuncture （ EA ） at Fengchi （ GB 20 ） on the microglial P2X4R - BDNF pathway of the trigeminal caudal nucleus （ TNC ） in rat models of chronic migraine （ CM ） . Methods A total of 24 Sprague - Dawley rats were ran‐ domly allocated into three groups （ n=8/group ）： the blank control group ， the model control group and the EA group. A rat model of CM was established by repeated subcutaneous injections of nitroglycerin （ NTG ） . EA was administered bilaterally at the GB20 acupoints once daily for 10 consecutive days. Mechanical pain threshold was evaluated using the paw withdrawal threshold measured with an elec‐ tronic von Frey filament. Immunofluorescence （ IF ） and Western blot （ WB ） were used to detect the expression of Iba1labeled microglia ， P2X4R ， BDNF ， p - p38 MAPK ， p - ERK ， c - Fos and CGRP in the TNC. Results Compared with the blank control group ， the model con‐ trol group exhibited a significant decrease in mechanical pain threshold （ P < 0. 0001 ）， along with varying degrees of upregulation in the expression of Iba1 ， P2X4R ， BDNF ， p - p38 MAPK ， p - ERK ， c - Fos ， and CGRP in the TNC （ P < 0. 01 ） . In contrast ， compared with the model control group ， the EA group showed a significant increase in mechanical pain hypersensitivity （ P < 0. 0001 ） and varying degrees of downregulation in the expression of Iba1 ， P2X4R ， BDNF ， p - p38 MAPK ， p - ERK ， c - Fos ， and CGRP in the TNC （ P < 0. 05 ） . Con⁃ clusions Our results demonstrate that EA alleviates CM hyperalgesia in a repeated NTG injection model. The analgesic effect is associ‐ ated with the suppression of microglial activation and its P2X4R - BDNF signaling in the TNC.