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Electroacupuncture Regulates Pain Transition by Inhibiting the mGluR5-PKCε Signaling Pathway in the Dorsal Root Ganglia.
J Pain Res. 2020; 13:1471-1483.JP

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.

Authors+Show Affiliations

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.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.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.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.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.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.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.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.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.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32606913

Citation

Wang, Sisi, et al. "Electroacupuncture Regulates Pain Transition By Inhibiting the mGluR5-PKCε Signaling Pathway in the Dorsal Root Ganglia." Journal of Pain Research, vol. 13, 2020, pp. 1471-1483.
Wang S, Du J, Shao F, et al. Electroacupuncture Regulates Pain Transition by Inhibiting the mGluR5-PKCε Signaling Pathway in the Dorsal Root Ganglia. J Pain Res. 2020;13:1471-1483.
Wang, S., Du, J., Shao, F., Wang, W., Sun, H., Shao, X., Liang, Y., Liu, B., Fang, J., & Fang, J. (2020). Electroacupuncture Regulates Pain Transition by Inhibiting the mGluR5-PKCε Signaling Pathway in the Dorsal Root Ganglia. Journal of Pain Research, 13, 1471-1483. https://doi.org/10.2147/JPR.S251948
Wang S, et al. Electroacupuncture Regulates Pain Transition By Inhibiting the mGluR5-PKCε Signaling Pathway in the Dorsal Root Ganglia. J Pain Res. 2020;13:1471-1483. PubMed PMID: 32606913.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Electroacupuncture Regulates Pain Transition by Inhibiting the mGluR5-PKCε Signaling Pathway in the Dorsal Root Ganglia. AU - Wang,Sisi, AU - Du,Junying, AU - Shao,Fangbing, AU - Wang,Wen, AU - Sun,Haiju, AU - Shao,Xiaomei, AU - Liang,Yi, AU - Liu,Boyi, AU - Fang,Jianqiao, AU - Fang,Junfan, Y1 - 2020/06/19/ PY - 2020/02/29/received PY - 2020/05/27/accepted PY - 2020/7/2/entrez PY - 2020/7/2/pubmed PY - 2020/7/2/medline KW - DRGs KW - PKCε KW - electroacupuncture KW - hyperalgesic priming KW - mGluR5 KW - pain transition SP - 1471 EP - 1483 JF - Journal of pain research JO - J Pain Res VL - 13 N2 - 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. SN - 1178-7090 UR - https://www.unboundmedicine.com/medline/citation/32606913/Electroacupuncture_Regulates_Pain_Transition_by_Inhibiting_the_mGluR5-PKCε_Signaling_Pathway_in_the_Dorsal_Root_Ganglia L2 - https://dx.doi.org/10.2147/JPR.S251948 DB - PRIME DP - Unbound Medicine ER -
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