Dorsal root ganglia P2X4 and P2X7 receptors contribute to diabetes-induced hyperalgesia and the downregulation of electroacupuncture on P2X4 and P2X7

Hu, Qunqi; He, Xiaofen; Ma, Yiqi; Ma, Liqian; Qu, Siying; Wang, Han-Zhi; Kang, Yu-Rong; Chen, Luhang; Li, Xiang; Liu, Boyu; Shao, Xiaomei; Fang, Jiaqi; Liang, Yi; Jiang, Yongliang

doi:10.1007/s11302-022-09844-8

Cited by 12 publications

(9 citation statements)

References 52 publications

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“…Numerous studies have shown that EA intervention on ST36 and BL60 in rats can alleviate diferent types of neuropathic pain [56][57][58]. Te preliminary study of our research group showed that the intervention of EA of ST36 and BL60 can efectively alleviate diabetic neuropathic pain [59,60]. Tus, in the present study, the acupoints of ST36 and BL60 were selected to study the analgesic mechanism of EA.…”

Section: Discussionmentioning

confidence: 84%

Electroacupuncture Alleviates Diabetic Neuropathic Pain and Downregulates p‐PKC and TRPV1 in Dorsal Root Ganglions and Spinal Cord Dorsal Horn

Kang

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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Diabetic neuropathic pain (DNP) is a common complication of diabetes. Streptozotocin (STZ)-induced changes of protein in dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) are critical for DNP genesis. However, which proteins change remains elusive. Here, the DNP model was established by a single intraperitoneal injection of STZ, accompanied by increased fasting blood glucose (FBG), decreased body weight (BW), and decreased paw withdrawal latency (PWL). Proteins change in L4-L6 DRGs and SCDH of rats were detected. Western blot and immunofluorescence results showed that expression levels of phosphorylated protein kinase C (p-PKC), transient receptor potential vanilloid-1 (TRPV1), Substance P (SP) and calcitonin gene-related peptide (CGRP) in the DRG and the SCDH of rats were increased after STZ injection. A preliminary study from our previous study showed that 2 Hz electroacupuncture (EA) effectively alleviates DNP. However, the analgesic mechanism of EA needs further elucidation. Here, EA at the bilateral Zusanli (ST36) and KunLun (BL60) acupoints was applied for one week, and to investigate the effect on DNP. EA reversed thermal hyperalgesia in DNP rats and downregulated the expression of p-PKC, TRPV1, SP, and CGRP in DRG and SCDH.

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Section: Discussionmentioning

confidence: 84%

Electroacupuncture Alleviates Diabetic Neuropathic Pain and Downregulates p‐PKC and TRPV1 in Dorsal Root Ganglions and Spinal Cord Dorsal Horn

Kang

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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“…Similarly, electroacupuncture treatment was found to mitigate P2X7R expression, alleviating neuroinflammation and pain. 27,80,81 Last but not least, reduced pain sensitivity has been documented in P2X7R knockout mice, 56,82,83 demonstrating the necessity of P2X7R in neuropathic pain.…”

Section: The Function Of Microglial P2x7r In Neuropathic Painmentioning

confidence: 97%

“…P2X7R was first discovered in 1998, pinpointing its location near human chromosome 12q24 26 . It represents the seventh isoform of the P2X receptors and is unique among this protein family in that it is dependent on adenosine 5′‐triphosphate (ATP) non‐selective cation channel 27 . Comprising three primary domains, 10,28,29 P2X7R includes an extracellular loop, the ATP binding site, and two structural transmembrane domains (TM1 and TM2), accountable for regulating the ion channel's opening.…”

Section: An Overview Of P2x7rmentioning

confidence: 99%

Involvement of microglial P2X7 receptor in pain modulation

Zhang,

Gao,

Zhang

et al. 2023

CNS Neurosci Ther

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BackgroundPain is a rapid response mechanism that compels organisms to retreat from the harmful stimuli and triggers a repair response. Nonetheless, when pain persists for extended periods, it can lead to adverse changes into in the individual’s brain, negatively impacting their emotional state and overall quality of life. Microglia, the resident immune cells in the central nervous system (CNS), play a pivotal role in regulating a variety of pain‐related disorders. Specifically, recent studies have shed light on the central role that microglial purinergic ligand‐gated ion channel 7 receptor (P2X7R) plays in regulating pain. In this respect, the P2X7R on microglial membranes represents a potential therapeutic target.AimsTo expound on the intricate link between microglial P2X7R and pain, offering insights into potential avenues for future research.MethodsWe reviewed 140 literature and summarized the important role of microglial P2X7R in regulating pain, including the structure and function of P2X7R, the relationship between P2X7R and microglial polarization, P2X7R‐related signaling pathways, and the effects of P2X7R antagonists on pain regulation.ResultsP2X7R activation is related to M1 polarization of microglia, while suppressing P2X7R can transfer microglia from M1 into M2 phenotype. And targeting the P2X7R‐mediated signaling pathways helps to explore new therapy for pain alleviation. P2X7R antagonists also hold potential for translational and clinical applications in pain management.ConclusionsMicroglial P2X7R holds promise as a potential novel pharmacological target for clinical treatments due to its distinctive structure, function, and the development of antagonists.

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“…The protein levels of P2X4 and P2X7 in diabetes-induced neuropathy rats were significantly increased. 2 Hz EA improved the paw withdrawal latency and reduced the expression of P2X4 and P2X7 in DRG ( Hu et al, 2022 ). EA attenuated Na v 1.7 and Na v 1.8 protein expression levels in the DRG during painful states ( Yen et al, 2018 ).…”

Section: Acupuncture Mechanisms On Neuropathic Painmentioning

confidence: 98%

Potential mechanisms of acupuncture for neuropathic pain based on somatosensory system

Chen

Yang

et al. 2022

Front. Neurosci.

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Neuropathic pain, caused by a lesion or disease of the somatosensory system, is common and distressing. In view of the high human and economic burden, more effective treatment strategies were urgently needed. Acupuncture has been increasingly used as an adjuvant or complementary therapy for neuropathic pain. Although the therapeutic effects of acupuncture have been demonstrated in various high-quality randomized controlled trials, there is significant heterogeneity in the underlying mechanisms. This review aimed to summarize the potential mechanisms of acupuncture on neuropathic pain based on the somatosensory system, and guided for future both foundational and clinical studies. Here, we argued that acupuncture may have the potential to inhibit neuronal activity caused by neuropathic pain, through reducing the activation of pain-related ion channels and suppressing glial cells (including microglia and astrocytes) to release inflammatory cytokines, chemokines, amongst others. Meanwhile, acupuncture as a non-pharmacologic treatment, may have potential to activate descending pain control system via increasing the level of spinal or brain 5-hydroxytryptamine (5-HT), norepinephrine (NE), and opioid peptides. And the types of endogenously opioid peptides was influenced by electroacupuncture-frequency. The cumulative evidence demonstrated that acupuncture provided an alternative or adjunctive therapy for neuropathic pain.

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Dorsal root ganglia P2X4 and P2X7 receptors contribute to diabetes-induced hyperalgesia and the downregulation of electroacupuncture on P2X4 and P2X7

Cited by 12 publications

References 52 publications

Electroacupuncture Alleviates Diabetic Neuropathic Pain and Downregulates p‐PKC and TRPV1 in Dorsal Root Ganglions and Spinal Cord Dorsal Horn

Electroacupuncture Alleviates Diabetic Neuropathic Pain and Downregulates p‐PKC and TRPV1 in Dorsal Root Ganglions and Spinal Cord Dorsal Horn

Involvement of microglial P2X7 receptor in pain modulation

Potential mechanisms of acupuncture for neuropathic pain based on somatosensory system

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