Electroacupuncture Stimulation Alleviates CFA-Induced Inflammatory Pain Via Suppressing P2X3 Expression

Xiang, Xuaner; Wang, Sisi; Shao, Fangbing; Fang, Jiaqi; Xu, Yang; Wang, Wen; Sun, Haiju; Liu, Xiao Dong; Du, Junying; Fang, Jianqiao

doi:10.3390/ijms20133248

Cited by 73 publications

(56 citation statements)

References 42 publications

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“…Electroacupuncture (EA) is widely used to treat chronic pain, including diabetes-associated pain [26][27][28]. Mounting evidence in animal models indicates involvement of P2X3 receptor in neuropathic pain [29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture alleviates diabetic neuropathic pain in rats by suppressing P2X3 receptor expression in dorsal root ganglia

Fei

Tai

et al. 2020

Purinergic Signalling

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Diabetic neuropathic pain (DNP) is a troublesome diabetes complication all over the world. P2X3 receptor (P2X3R), a purinergic receptor from dorsal root ganglion (DRG), has important roles in neuropathic pain pathology and nociceptive sensations. Here, we investigated the involvement of DRG P2X3R and the effect of 2 Hz electroacupuncture (EA) on DNP. We monitored the rats’ body weight, fasting blood glucose level, paw withdrawal thresholds, and paw withdrawal latency, and evaluated P2X3R expression in DRG. We found that P2X3R expression is upregulated on DNP, while 2 Hz EA is analgesic against DNP and suppresses P2X3R expression in DRG. To evaluate P2X3R involvement in pain modulation, we then treated the animals with A317491, a P2X3R specific antagonist, or α β-me ATP, a P2X3R agonist. We found that A317491 alleviates hyperalgesia, while α β-me ATP blocks EA’s analgesic effects. Our findings indicated that 2 Hz EA alleviates DNP, possibly by suppressing P2X3R upregulation in DRG.

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Section: Introductionmentioning

confidence: 99%

Electroacupuncture alleviates diabetic neuropathic pain in rats by suppressing P2X3 receptor expression in dorsal root ganglia

Fei

Tai

et al. 2020

Purinergic Signalling

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“…Related studies have shown that the therapeutic effect of EA on pain is closely related to its intervention in the peripheral nervous systems. [32][33][34] A previous study demonstrated that the therapeutic effect of EA on chronic pain is partially achieved by regulating the PKCε signal transduction pathway. 35,36 EA can also exert its analgesic effect by regulating the expression of mGluR5 in the DRG.…”

Section: Introductionmentioning

confidence: 99%

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

Wang¹,

Du²,

Shao³

et al. 2020

JPR

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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.

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“…It was noted that 100 Hz EAP stimulation had a stronger effect than stimulation with 2 Hz. In addition, EAP reversed the increased P2X3R-immunoreactivity and protein expression in DRGs, as measured by quantitative immunohistochemistry and western blotting, respectively [44,45].…”

Section: P2x3 Receptorsmentioning

confidence: 92%

“…When the PWT and PWL were measured with mechanical pressure and heat, respectively, on the CFA-treated hind paw of rats, EAP applied to Zusanli and BL60 (Kunlun acupoint) exerted analgesia in this inflammatory pain model [44,45]. It was noted that 100 Hz EAP stimulation had a stronger effect than stimulation with 2 Hz.…”

Section: P2x3 Receptorsmentioning

confidence: 99%

Purinergic signaling as a basis of acupuncture-induced analgesia

Tang

et al. 2020

Purinergic Signalling

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This review summarizes experimental evidence indicating that purinergic mechanisms are causally involved in acupuncture (AP)-induced analgesia. Electroacupuncture (EAP) and manual AP release at pain-relevant acupoints ATP which may activate purinergic P2X receptors (Rs) especially of the P2X3 type situated at local sensory nerve endings (peripheral terminals of dorsal root ganglion [DRG] neurons); the central processes of these neurons are thought to inhibit via collaterals of ascending dorsal horn spinal cord neurons, pain-relevant pathways projecting to higher centers of the brain. In addition, during AP/EAP non-neuronal P2X4 and/or P2X7Rs localized at microglial cells of the CNS become activated at the spinal or supraspinal levels. In consequence, these microglia secrete bioactive compounds such as growth factors, cytokines, chemokines, reactive oxygen, and nitrogen species, which modulate the ascending neuronal pathways conducting painful stimuli. Alternatively, ATP released at acupoints by AP/EAP may be enzymatically degraded to adenosine, stimulating in loco presynaptic A1Rs exerting an inhibitory influence on the primary afferent fibers (the above mentioned pain-sensing peripheral terminals of DRG neurons) which thereby fail to conduct action potentials to the spinal cord dorsal horn. The net effect of the stimulation of P2X3, P2X4, P2X7, and A1Rs by the AP/EAP-induced release of ATP/adenosine at certain acupoints will be analgesia.

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Electroacupuncture Stimulation Alleviates CFA-Induced Inflammatory Pain Via Suppressing P2X3 Expression

Cited by 73 publications

References 42 publications

Electroacupuncture alleviates diabetic neuropathic pain in rats by suppressing P2X3 receptor expression in dorsal root ganglia

Electroacupuncture alleviates diabetic neuropathic pain in rats by suppressing P2X3 receptor expression in dorsal root ganglia

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

Purinergic signaling as a basis of acupuncture-induced analgesia

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