电针通过抑制背根神经节中的mGluR5-PKCε信号通路调节疼痛转换。
Electroacupuncture Regulates Pain Transition by Inhibiting the mGluR5-PKCε Signaling Pathway in the Dorsal Root Ganglia.
作者信息
Wang Sisi, Du Junying, Shao Fangbing, Wang Wen, Sun Haiju, Shao Xiaomei, Liang Yi, Liu Boyi, Fang Jianqiao, Fang Junfan
机构信息
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.
出版信息
J Pain Res. 2020 Jun 19;13:1471-1483. doi: 10.2147/JPR.S251948. eCollection 2020.
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.
背景
急性疼痛可转变为慢性疼痛，这是一个重大的临床挑战。电针（EA）可部分预防急性疼痛向慢性疼痛的转变。然而，关于EA作用的潜在机制知之甚少。本研究调查了EA对疼痛转变以及背根神经节（DRG）中代谢型谷氨酸受体5（mGluR5）-蛋白激酶Cε（PKCε）信号通路激活的影响。
方法
通过在大鼠左后爪足底依次注射角叉菜胶（1%，100μL）和前列腺素E2（PGE2）建立痛觉过敏启动模型。对大鼠双侧足三里（ST36）和昆仑（BL60）穴位进行EA治疗（2/100Hz，30分钟，每天一次）。使用von Frey细丝在不同时间点检测机械缩足阈值（MWT）。通过蛋白质免疫印迹法检测大鼠同侧L4-L6 DRG中mGluR5和PKCε的蛋白表达水平。进行了一些药理学实验以评估mGluR5、PKCε与MWT之间的关系。还用于测试EA对mGluR5和PKCε表达水平以及MWT变化的影响。
结果
依次注射角叉菜胶和PGE2显著降低了大鼠的MWT，并上调了同侧L4-L6 DRG中mGluR5和PKCε的表达水平。EA可逆转依次注射角叉菜胶/PGE2诱导的痛觉过敏启动，并下调mGluR5和PKCε的蛋白表达。注射谷氨酸而非PGE2可模拟痛觉过敏启动模型。用特异性拮抗剂MTEP对mGluR5进行药理学阻断可预防痛觉过敏启动并抑制DRG中PKCε的激活。此外，EA对角叉菜胶/mGluR5注射诱导的痛觉过敏启动大鼠也产生镇痛作用，并抑制PKCε的高表达。假针刺无镇痛和调节作用。
结论
EA可调节疼痛转变，这可能与其对DRG中mGluR5-PKCε信号通路激活的抑制作用有关。
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