Electro-acupuncture inhibits C-fiber-evoked WDR neuronal activity of the trigeminocervical complex: Neurophysiological hypothesis of a complementary therapy for acute migraine modeled rats

Qu, Zhengyang; Liu, Lu; Yang, Yi; Zhao, Luopeng; Xu, Xiaobai; Li, Zhijuan; Zhu, Yupu; Jing, Xiang-Hong; Wang, Xiaoyu; Zhang, Claire Shuiqing; Fisher, Marc; Li, Bin; Wang, Linpeng

doi:10.1016/j.brainres.2020.146670

Cited by 17 publications

(20 citation statements)

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“…The protocols used for the dural cannulation were similar to those described previously ( Boyer et al, 2017 ; Qu et al, 2020a ). A previous study found that the effects of inflammatory soup (IS) application on the dura was due to the activation of trigeminal afferents and not to a systemic ( Boyer et al, 2014 ).…”

Section: Methodsmentioning

confidence: 99%

“…p-PKA and p-ERK are considered to be the key to activate nociceptive neurons and maintain peripheral and central sensitization ( Giniatullin et al, 2008 ; Iwashita et al, 2013 ; Nakaya et al, 2016 ). Our previous investigation found EA shows a direct effect on nociceptive neurons ( Qu et al, 2020a , b ). In addition, several studies ( Han et al, 2015 ; Shao et al, 2016 ; Hu et al, 2020 ) suggested PKA and ERK 1 / 2 in the spinal dorsal horn might involve EA antihyperalgesia.…”

Section: Introductionmentioning

confidence: 91%

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Determining 5HT7R’s Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine

Liu

et al. 2021

Front. Neurosci.

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Electroacupuncture (EA) is widely used in clinical practice to relieve migraine pain. 5-HT7 receptor (5-HT7R) has been reported to play an excitatory role in neuronal systems and regulate hyperalgesic pain and neurogenic inflammation. 5-HT7R could influence phosphorylation of protein kinase A (PKA)- or extracellular signal-regulated kinase1/2 (ERK1/2)-mediated signaling pathways, which mediate sensitization of nociceptive neurons via interacting with cyclic adenosine monophosphate (cAMP). In this study, we evaluated the role of 5-HT7R in the antihyperalgesic effects of EA and the underlying mechanism through regulation of PKA and ERK1/2 in trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC). Hyperalgesia was induced in rats with dural injection of inflammatory soup (IS) to cause meningeal neurogenic inflammatory pain. Electroacupuncture was applied for 15 min every other day before IS injection. Von Frey filaments, tail-flick, hot-plate, and cold-plated tests were used to evaluate the mechanical and thermal hyperalgesia. Neuronal hyperexcitability in TNC was studied by an electrophysiological technique. The 5-HT7R antagonist (SB269970) or 5-HT7R agonist (AS19) was administered intrathecally before each IS application at 2-day intervals during the 7-day injection protocol. The changes in 5-HT7R and 5-HT7R-associated signaling pathway were examined by real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) analyses. When compared with IS group, mechanical and thermal pain thresholds of the IS + EA group were significantly increased. Furthermore, EA prevented the enhancement of both spontaneous activity and evoked responses of second-order trigeminovascular neurons in TNC. Remarkable decreases in 5-HT7R mRNA expression and protein levels were detected in the IS + EA group. More importantly, 5-HT7R agonist AS19 impaired the antihyperalgesic effects of EA on p-PKA and p-ERK1/2. Injecting 5-HT7R antagonist SB-269970 into the intrathecal space of IS rats mimicked the effects of EA antihyperalgesia and inhibited p-PKA and p-ERK1/2. Our findings indicate that 5-HT7R mediates the antihyperalgesic effects of EA on IS-induced migraine pain by regulating PKA and ERK1/2 in TG and TNC.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Determining 5HT7R’s Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine

Liu

et al. 2021

Front. Neurosci.

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“…Acupuncture analgesia is thought to be partially achieved by A-fiber-mediated “gate” control of noxious inputs ( Zhao, 2008 ). It has been reported that electroacupuncture (EA) could modulate somatic afferents to inhibit the noxious WDR neuronal activity in migraine rats ( Qu et al, 2020 ). Therefore, these findings provide a possibility that EA with low intensity may attenuate WDR neuron-mediated pain transmission by activating LTM neurons.…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture-Induced Muscular Inflammatory Pain Relief Was Associated With Activation of Low-Threshold Mechanoreceptor Neurons and Inhibition of Wide Dynamic Range Neurons in Spinal Dorsal Horn

et al. 2021

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Acupuncture is an effective alternative therapy for pain management. Evidence suggests that acupuncture relieves pain by exciting somatic afferent nerve fibers. However, the mechanism underlying the interaction between neurons in different layers of the spinal dorsal horn induced by electroacupuncture (EA) remains unclear. The aim of this study was to explore the mechanism of EA relieving inflammatory muscle pain, which was associated with activation of the spontaneous firing of low-threshold mechanoreceptor (LTM) neurons and inhibition of wide dynamic range (WDR) neuronal activities in the spinal dorsal horn of rats. Inflammatory muscle pain was induced by injecting complete Freund’s adjuvant into the right biceps femoris muscle. EA with intensity of threshold of A fibers (Ta) in Liangqiu (ST34) muscle considerably inhibited the abnormal spontaneous activities of electromyography (EMG) due to muscle inflammation. While EA with intensity of C-fiber threshold (Tc) increased the abnormal activities of EMG. EA with Ta also ameliorated the imbalance of weight-bearing behavior. A microelectrode array with 750-μm depth covering 32 channels was used to record the neuronal activities of WDR and LTM in different layers of the spinal dorsal horn. The spontaneous firing of LTM neurons was enhanced by EA-Ta, while the spontaneous firing of WDR neurons was inhibited. Moreover, EA-Ta led to a significant inverse correlation between changes in the frequency of WDR and LTM neurons (r = −0.64, p < 0.05). In conclusion, the results indicated that EA could alleviate inflammatory muscle pain, which was associated with facilitation of the spontaneous firing of LTM neurons and inhibition of WDR neuronal activities. This provides a promising evidence that EA-Ta could be applied to relieve muscular inflammatory pain in clinical practice.

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“…The protocols used for the dural cannulation were similar to those described previously [13,23]. A previous study found that the effects of in ammatory soup (IS) application on the dura were due to the activation of trigeminal afferents and not to a systemic [48].…”

Section: Dural Cannulation and In Ammatory Soup Injectionmentioning

confidence: 99%

“…p-PKA and p-ERK are considered to be the key to activate nociceptive neurons, and maintain peripheral and central sensitization [10,21,22]. Our previous investigation found EA shows a direct effect on nociceptive neurons [23,24]. In addition, several studies [25][26][27] suggested PKA and ERK 1/2 in the spinal dorsal horn might involve EA antihyperalgesia.…”

Section: Introductionmentioning

confidence: 96%

Determining 5HT7R’s involvement in modifying the antihyperalgesic effects of electroacupuncture on rats with recurrent migraine

Liu

et al. 2020

Preprint

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Background: Electroacupuncture (EA) is widely used in clinical practice to relieve migraine pain. 5-HT7 receptor (5-HT7R) has been reported to play an excitatory role in neuronal systems and regulate hyperalgesic pain and neurogenic inflammation. 5-HT7R could influence Phosphorylation of protein kinase A (PKA)- or Extracellular signal-regulated kinase1/2 (ERK1/2)-mediated signaling pathways, which mediate sensitization of nociceptive neurons via interacting with cyclic Adenosine monophosphate (cAMP). In this study, we evaluated the role of 5-HT7R in the antihyperalgesic effects of EA and the underlying mechanism through regulation of PKA and ERK1/2 in trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC). Methods: Hyperalgesia was induced in rats with dural injection of inflammatory soup (IS) to cause meningeal neurogenic inflammatory pain. Electroacupuncture was applied for 15 minutes every other day before IS injection. Von Frey filaments, tail-flick, hot-plate, and cold-plated tests were used to evaluate the mechanical and thermal hyperalgesia. Neuronal hyperexcitability in TNC was studied by an electrophysiological technique. The 5-HT7R antagonist (SB269970) or 5-HT7R agonist (AS19) was administered intrathecally before each IS application at 2-days intervals during the 7-days injection protocol. The changes in 5-HT7R and 5-HT7R-mediated signaling pathway were examined by real time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence and enzyme-linked immunosorbent assay (ELISA) analyses.Results: When compared with IS group, mechanical and thermal pain thresholds of the IS+EA group were significantly increased. Furthermore, EA prevented the enhancement of both spontaneous activity and evoked responses of second-order trigeminovascular neurons in TNC. Remarkable decreases in 5-HT7R mRNA expression and protein levels were detected in the IS+EA group. More importantly, 5-HT7R agonist AS19 impaired the antihyperalgesic effects of EA on p-PKA and p-ERK1/2. Injecting 5-HT7R antagonist SB-269970 into the intrathecal space of IS rats mimicked the effects of EA antihyperalgesia and inhibited p-PKA and p-ERK1/2. Conclusion: Our findings indicate that 5-HT7R mediates the antihyperalgesic effects of EA on IS-induced migraine pain by regulating PKA and ERK1/2 in TG and TNC.

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Electro-acupuncture inhibits C-fiber-evoked WDR neuronal activity of the trigeminocervical complex: Neurophysiological hypothesis of a complementary therapy for acute migraine modeled rats

Cited by 17 publications

References 49 publications

Determining 5HT7R’s Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine

Determining 5HT7R’s Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine

Electroacupuncture-Induced Muscular Inflammatory Pain Relief Was Associated With Activation of Low-Threshold Mechanoreceptor Neurons and Inhibition of Wide Dynamic Range Neurons in Spinal Dorsal Horn

Determining 5HT7R’s involvement in modifying the antihyperalgesic effects of electroacupuncture on rats with recurrent migraine

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Electro-acupuncture inhibits C-fiber-evoked WDR neuronal activity of the trigeminocervical complex: Neurophysiological hypothesis of a complementary therapy for acute migraine modeled rats

Cited by 17 publications

References 49 publications

Determining 5HT7R’s Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine

Determining 5HT7R’s Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine

Electroacupuncture-Induced Muscular Inflammatory Pain Relief Was Associated With Activation of Low-Threshold Mechanoreceptor Neurons and Inhibition of Wide Dynamic Range Neurons in Spinal Dorsal Horn

Determining 5HT7R’s involvement in modifying the antihyperalgesic effects of&nbsp;electroacupuncture on rats with recurrent migraine

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Determining 5HT7R’s involvement in modifying the antihyperalgesic effects of electroacupuncture on rats with recurrent migraine