Electroacupuncture alleviates morphine‑induced hyperalgesia by regulating spinal CB1 receptors and ERK1/2 activity

Zheng,Yuxin; Yu,Yang; Xie,Keliang; Yuan,Yuan; Chen,Yi; Wang,Chunyan; Wang,Guolin; Yu,Yonghao

doi:10.3892/mmr.2019.10329

Electroacupuncture alleviates morphine‑induced hyperalgesia by regulating spinal CB1 receptors and ERK1/2 activity

Authors:
- Yuxin Zheng
- Yang Yu
- Keliang Xie
- Yuan Yuan
- Yi Chen
- Chunyan Wang
- Guolin Wang
- Yonghao Yu
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Affiliations: Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
Published online on: June 4, 2019 https://doi.org/10.3892/mmr.2019.10329
Pages: 1113-1120
Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Electroacupuncture (EA), a traditional Chinese therapeutic technique, is considered an effective method for treating certain painful neuropathies induced by various neuropathological damage. The current study investigated the effect of EA on intrathecal (IT) morphine‑induced hyperalgesia (MIH) and examined the hypothesis that activation of cannabinoid receptor 1 (CB1) could enhance the antinociceptive effect of EA on MIH via regulation of the extracellular signal‑regulated kinase 1/2 (ERK1/2) signaling pathway. Using a rat model of IT MIH, mechanical and thermal hyperalgesia were evaluated by an electronic von Frey filament and hotplate at baseline (1 day before IT administration) and at days 1, 3, 5 and 7 after IT administration. Rats received IT normal saline, IT morphine or IT morphine + EA at ST36‑GB34. The protein levels of ERK1/2, phosphorylated (p)‑ERK1/2 and CB1 in the spinal cord were assayed by western blotting. Furthermore, the effect of IT injection of the CB1 agonist WIN 55,212‑2 and the CB1 antagonist SR141716 on the antinociceptive effect of EA in rats with MIH was investigated. Nociceptive behavior and ERK1/2, phosphorylated (p)‑ERK1/2 and CB1 protein levels were evaluated as mentioned above. The results revealed that chronic IT injections of morphine induced a significant decrease in mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) accompanied with remarkable upregulation of p‑ERK1/2 in the spinal cord, which could be attenuated by EA at the ST36‑GB34 acupoints. In the rat model of MIH, IT injection of WIN 55,212‑2 combined with EA induced a significant increase in MWT and TWL accompanied with a significant decrease in p‑ERK1/2 and a significant increase in CB1 protein level compared with EA alone, while SR141716 induced the opposite results. The present study suggests that EA alleviates hyperalgesia induced by IT injection of morphine partially through the inhibition of ERK1/2 activation. Activation of the CB1 receptor enhances the antinociceptive effect of EA in rats with MIH partly through the regulation of the spinal CB1‑ERK1/2 signaling pathway.

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