Neuregulin1-ErbB4 Signaling in Spinal Cord Participates in Electroacupuncture Analgesia in Inflammatory Pain

Wan, Chaofan; Xu, Yunlong; Cen, Baoyan; Xia, Yucen; Yao, Lin; Zheng, Yao; Zhao, Jiaying; Su, He; Chen, Yongjun

doi:10.3389/fnins.2021.636348

Cited by 12 publications

(9 citation statements)

References 56 publications

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“…Electroacupuncture is an effective and safe alternative therapy for treating anxiety disorders ( Errington-Evans, 2012 ). Studies have shown that EA at the Zusanli and Sanyinjiao acupoints can reduce the mechanical and thermal pain sensitivities of inflammatory pain induced by CFA in mice models ( Wan et al, 2021 ). Acupuncture of the Zusanli acupoint can improve motor function and anxiety-like behavior in Parkinson’s disease mice models ( Jang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury

Zhu

Shen

et al. 2022

Front. Neurosci.

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Neuropathic pain is a common cause of chronic pain and is often accompanied by negative emotions, making it complex and difficult to treat. However, the neural circuit mechanisms underlying these symptoms remain unclear. Herein, we present a novel pathway associated with comorbid chronic pain and anxiety. Using chemogenetic methods, we found that activation of glutamatergic projections from the rostral anterior cingulate cortex (rACCGlu) to the ventrolateral periaqueductal gray (vlPAG) induced both hyperalgesia and anxiety-like behaviors in sham mice. Inhibition of the rACCGlu-vlPAG pathway reduced anxiety-like behaviors and hyperalgesia in the spared nerve injury (SNI) mice model; moreover, electroacupuncture (EA) effectively alleviated these symptoms. Investigation of the related mechanisms revealed that the chemogenetic activation of the rACCGlu-vlPAG circuit effectively blocked the analgesic effect of EA in the SNI mice model but did not affect the chronic pain-induced negative emotions. This study revealed a novel pathway, the rACCGlu-vlPAG pathway, that mediates neuropathic pain and pain-induced anxiety.

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Section: Discussionmentioning

confidence: 99%

Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury

Zhu

Shen

et al. 2022

Front. Neurosci.

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“…ERBB4 encodes a receptor tyrosine kinase and promotes inhibitory synapse formation in pyramidal neurons 49 . ERBB4 mediates amyloid β-induced neurotoxicity, which is a biomarker for Alzheimer’s disease 50 , and Neuregulin1-ERBB4 signaling regulates the inflammatory pain of electroacupuncture analgesia in the spinal cord 51 . Moreover, the function of ERBB4 in dopamine neurons is related to depression-like behaviors, and it regulates the homeostasis of extracellular dopamine and norepinephrine in catecholaminergic cells 52 .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study identified six loci associated with adverse drug reactions to aripiprazole in schizophrenia patients

Wang

Mei

et al. 2023

Schizophr

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Aripiprazole is recommended for routine use in schizophrenia patients. However, the biological mechanism for the adverse drug reactions (ADRs) among schizophrenia patients with the antipsychotic drug aripiprazole is far from clear. To explore the potential genetic factors that may cause movement-related adverse antipsychotic effects in patients, we conducted an association analysis between movement-related ADRs and SNPs in schizophrenia patients receiving aripiprazole monotherapy. In this study, multiple ADRs of 384 patients were quantified within 6-week treatment, and the scores of movement-related ADRs at baseline and follow-up time points during treatment were obtained. The highest score record was used as the quantitative index in analysis, and genetic analysis at the genome-wide level was conducted. The SNP rs4149181 in SLC22A8 [P = 2.28 × 10−8] showed genome-wide significance, and rs2284223 in ADCYAP1R1 [P = 9.76 × 10−8], rs73258503 in KCNIP4 [P = 1.39 × 10−7], rs678428 in SMAD9 [P = 4.70 × 10−7], rs6421034 in NAP1L4 [P = 6.80 × 10−7], and rs1394796 in ERBB4 [P = 8.60 × 10−7] were found to be significantly associated with movement-related ADRs. The combined prediction model of these six loci showed acceptable performance in predicting adverse events [area under the curve (AUC): 0.84]. Combined with the function and network of the above genes and other candidate loci (KCNA1, CACNG1, etc.), we hypothesize that SLC22A8 and KCNIP4-Kv channel perform their respective functions as transporter or channel and participate in the in vivo metabolism or effects of aripiprazole. The above results imply the important function of ion transporters and channels in movement-related adverse antipsychotic effects in aripiprazole monotherapy schizophrenia patients.

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“…141 Some studies showed that EA can increase NRG1 expressions in muscles, proving that there is a potential relationship between EA and NRG1. 142,143 Wan et al 98 found that EA alleviated pain hypersensitivity because it increased NRG1 expressions in SC of CFA-induced inflammatory pain mice models. This analgesic effect was partly mediated by NRG1-ErbB4 signaling.…”

Section: Gabaergic Interneuronmentioning

confidence: 99%

Mechanisms of acupuncture–electroacupuncture on inflammatory pain

Zhang,

Zhou,

Huo

et al. 2023

Mol Pain

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Acupuncture, as a traditional treatment, has been extensively used in China for thousands of years. According to the World Health Organization (WHO), acupuncture is recommended for the treatment of 77 diseases. And sixteen of these diseases are related to inflammatory pain. As a combination of traditional acupuncture and modern electrotherapy, electroacupuncture (EA) has satisfactory analgesic effects on various acute and chronic pain. Because of its good analgesic effects and no side effects, acupuncture has been widely accepted all over the world. Despite the increase in the number of studies, the mechanisms via which acupuncture exerts its analgesic effects have not been conclusively established. A literature review of related research is of great significance to elaborate on its mechanisms and to inform on further research directions. We elucidated on its mechanisms of action on inflammatory pain from two levels: peripheral and central. It includes the mechanisms of acupuncture in the periphery (immune cells and neurons, purinergic pathway, nociceptive ion channel, cannabinoid receptor and endogenous opioid peptide system) and central nervous system (TPRV1, glutamate and its receptors, glial cells, GABAergic interneurons and signaling molecules ). In this review, we collected relevant recent studies to systematically explain the mechanisms of acupuncture in treating inflammatory pain, with a view to providing direction for future applications of acupuncture in inflammatory pain and promoting clinical development.

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Neuregulin1-ErbB4 Signaling in Spinal Cord Participates in Electroacupuncture Analgesia in Inflammatory Pain

Cited by 12 publications

References 56 publications

Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury

Rostral Anterior Cingulate Cortex–Ventrolateral Periaqueductal Gray Circuit Underlies Electroacupuncture to Alleviate Hyperalgesia but Not Anxiety-Like Behaviors in Mice With Spared Nerve Injury

Genome-wide association study identified six loci associated with adverse drug reactions to aripiprazole in schizophrenia patients

Mechanisms of acupuncture–electroacupuncture on inflammatory pain

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