Electroacupuncture Regulates Pain Transition by Inhibiting the mGluR5-PKCε Signaling Pathway in the Dorsal Root Ganglia

Sisi Wang; Junying Du; Fangbing Shao; Wen Wang; Haiju Sun; Xiaomei Shao; Yi Liang; Boyi Liu; Jianqiao Fang; Junfan Fang

doi:10.2147/JPR.S251948

Electroacupuncture Regulates Pain Transition by Inhibiting the mGluR5-PKCε Signaling Pathway in the Dorsal Root Ganglia

J Pain Res. 2020 Jun 19:13:1471-1483. doi: 10.2147/JPR.S251948. eCollection 2020.

Authors

Sisi Wang^#¹, Junying Du^#¹, Fangbing Shao¹, Wen Wang¹, Haiju Sun¹, Xiaomei Shao¹, Yi Liang¹, Boyi Liu¹, Jianqiao Fang¹, Junfan Fang¹

Affiliation

¹ Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou 310053, People's Republic of China.

^# Contributed equally.

Abstract

Background: Acute pain can transition to chronic pain, presenting a major clinical challenge. Electroacupuncture (EA) can partly prevent the transition from acute to chronic pain. However, little is known about the mechanisms underlying the effect of EA. This study investigated the effect of EA on pain transition and the activation of metabotropic glutamate receptor 5 (mGluR5)-protein kinase C epsilon (PKCε) signaling pathway in the dorsal root ganglia (DRG).

Methods: The hyperalgesic priming model was established by the sequential intraplantar injection of carrageenan (1%, 100 μL) and prostaglandin E2 (PGE2) into the left hind paw of rats. EA treatment (2/100 Hz, 30 min, once/day) was applied at bilateral Zusanli (ST36) and Kunlun (BL60) acupoints in rats. Von Frey filaments were used to investigate the mechanical withdrawal threshold (MWT) at different time points. The protein expression levels of mGluR5 and PKCε in the ipsilateral L4-L6 DRGs of rats were detected by Western blot. Some pharmacological experiments were performed to evaluate the relationship between mGluR5, PKCε and the MWT. It was also used to test the effects of EA on the expression levels of mGluR5 and PKCε and changes in the MWT.

Results: Sequential injection of carrageenan and PGE2 significantly decreased the MWT of rats and up-regulated the expression level of mGluR5 and PKCε in the ipsilateral L4-L6 DRGs. EA can reverse the hyperalgesic priming induced by sequential injection of carrageenan/PGE and down-regulate the protein expression of mGluR5 and PKCε. Glutamate injection instead of PGE2 can mimic the hyperalgesic priming model. Pharmacological blocking of mGluR5 with specific antagonist MTEP can prevent the hyperalgesic priming and inhibit the activation of PKCε in DRGs. Furthermore, EA also produced analgesic effect on the hyperalgesic priming rats induced by carrageenan/mGluR5 injection and inhibited the high expression of PKCε. Sham EA produced none analgesic and regulatory effect.

Conclusion: EA can regulate pain transition and it may relate with its inhibitory effect on the activation of mGluR5-PKCε signaling pathway in the DRGs.

Keywords: DRGs; PKCε; electroacupuncture; hyperalgesic priming; mGluR5; pain transition.

Grants and funding

The study was supported by grants from the National Natural Science Foundation of China (81603692, 81603690), the Zhejiang Provincial Natural Science Foundation China (LY19H270003, LY20H270006) and the Talent Project of Zhejiang Association for Science and Technology (2017YCGC004).