The Calcium Channel α2δ1 Subunit: Interactional Targets in Primary Sensory Neurons and Role in Neuropathic Pain

Cui, Weihong; Wu, Hongyun; Yu, Xiaowen; Song, Ting; Xu, Xinping; Xu, Fei

doi:10.3389/fncel.2021.699731

Cited by 20 publications

(15 citation statements)

References 108 publications

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“…The results showed an increase in the amplitude of action potentials in A-fibres of rat sural and vagal nerves upon oxaliplatin administration, indicating that oxaliplatin modulates Nav (83). calcium channels are known to be the key mediators involved in neuron sensitization (84). They play a critical role in neurotransmitter secretion by increasing the local calcium concentration in the pre-synaptic cell.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: The Molecular Signature Associated with Oxaliplatin Induced Peripheral Neuropathy in Colorectal Cancer

Modekurty

2024

Preprint

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Background: Oxaliplatin is the standard treatment option for colorectal cancer (CRC) which is one of the most prevalent forms of cancer. However, patients suffer either treatment discontinuation or adverse post-treatment life quality due to Oxaliplatin-induced peripheral neuropathy. Methods: Our study has comprehensively explored the molecular mechanisms underlying Oxaliplatin-induced peripheral neuropathy via an extensive literature survey and identified multiple genes that may contribute to neuropathy and neurotoxicity. In addition to that, the publicly available bulk transcriptomic data of Illumina HiSeq 2500 platform, comprising the CRC tissue of 18 individuals' tumor and adjacent normal tissue was processed to identify differentially expressed genes (DEGs). Moreover, the single-cell RNA sequencing data of 10X genomics comprising normal and tumor tissues was subjected to analysis using Seurat and sctype R packages to uncover the cancer cells associated DEGs. Functional and pathway enrichment analysis was conducted using the Genecodis4 web-based tool. Next, RNA-seq data of CRC cell lines treated with Oxaliplatin compared with normal individuals, was also processed and DEGs were determined to validate the inhibition of a curated list of neuropathy-associated genes. Results: From literature and database searches, a total of 1367 genes, including ion channel genes, normal sensory neuron-associated genes, and axon-excitability-related genes were collected that are either reported to be or may be contributing to neuropathy among cancer survivors upon oxaliplatin administration. The bulk transcriptomic data analysis revealed 715 DEGs and single-cell analysis uncovered 2,854 DEGs. Identified upregulated genes from single-cell data analysis, such as LGALS4, SPINK4, TFF3, REG4, and REG1A were found to be associated with tumor proliferation via epithelial-mesenchymal transitions, oxidative stress, dysregulated immune system, and inflammation which can be utilized as potential targets to devise novel therapeutic strategies for CRC treatment. Furthermore, many proteins involved in axon-excitability (NGF, SOD1, ROBO1, CNTNAP2, CNTNAP2, and KCNMB1), normal sensory neuron (SOX10, APOE, SST, S1PR1, and KCND3), voltage-gated sodium (SCNN1B, SCNN1G, SCNN1A, SCN1B, and SCN2B), calcium (CACNA2D2, CACNA1A, CACNA1C, CACNA1E, and CACNA1F), and potassium channels (KCND3, KCNMB1, KCNMA1, KCNJ2, and KCNN4) showed downregulation due to the oxaliplatin administration in CRC cell lines and their inhibition may have led to neuropathy which needs further validations. Conclusion: Our study uncovers the downregulation of multiple genes upon oxaliplatin administration leading to neuropathy development and also elucidates potential therapeutic targets for better prognosis of CRC.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: The Molecular Signature Associated with Oxaliplatin Induced Peripheral Neuropathy in Colorectal Cancer

Modekurty

2024

Preprint

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“…The calcium signaling pathway of DRG is a key factor in the immediate analgesic effect of tuina. Many of the pathways enriched in this study were associated with cascade activation of the calcium signaling pathway, which is critical to initiate and maintain peripheral sensitization of NP ( Cui et al, 2021 ). Peripheral injurious stimuli increase intracellular Ca2 + through calcium signaling pathways, N -methyl- D -aspartic acid receptors, and other metabolic-like receptors in response to each other, and it can further activate calcium/calmodulin-dependent protein kinase II, and protein kinase A, which enhances postsynaptic excitability and triggers NP, resulting in peripheral and central sensitization ( Yang et al, 2004 ; Latremoliere and Woolf, 2009 ; Incontro et al, 2018 ; Liu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of immediate analgesic effect of 1-time tuina intervention in minor chronic constriction injury rats using RNA-seq

Wang

Liu

et al. 2022

Front. Neurosci.

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Previous studies have proved and investigated the mechanism of the analgesic effect of tuina treatment on neuropathic pain. The purpose of this study was to analyze changes in gene expression in the dorsal root ganglia (DRG) and spinal dorsal horn (SDH) after 1-time tuina intervention to investigate the immediate analgesic mechanism by tuina. An improvement in nociceptive behavior in minor chronic constriction injury (CCI) rats after 1-time tuina was observed. 1-time tuina was more effective in the amelioration of thermal hyperalgesia, but no changes were found in the ultrastructure of DRG and SDH. Sixty-five differentially expressed genes (DEGs) modulated by tuina were detected in the DRG and 123 DEGs were detected in the SDH. Potential immediate analgesic mechanisms of tuina were analyzed by the Kyoto Encyclopedia of Genes and Genomes. DEGs were enriched in 75 pathways in DRG, and 107 pathways in SDH. The immediate analgesic mechanism of tuina is related to the calcium signaling pathway, thermogenesis, and regulation of lipolysis in adipocytes.

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“…It acts as a target for the action of gabapentin. 53,54 Extrasynaptic GABAaR expression was downregulated in CPSP but a2d-1 subunit expression was upregulated; this may be related to abnormal electrical activity in the thalamus in patients with CPSP. 47,53,55 Blocking the protein-protein 1338 reaction of postsynaptic density protein 95 (PSD-95) and neuronal nitric oxide synthase (nNOS) before thalamic hemorrhage can alleviate the hemorrhage-induced thalamic pain.…”

Section: Thalamic Lesionsmentioning

confidence: 99%

Role of Sensory Pathway Injury in Central Post-Stroke Pain: A Narrative Review of Its Pathogenetic Mechanism

Li¹,

Lin²,

Tan³

et al. 2023

JPR

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Central post-stroke pain (CPSP) is a severe chronic neuropathic pain syndrome that is a direct result of cerebrovascular lesions affecting the central somatosensory system. The pathogenesis of this condition remains unclear owing to its extensive clinical manifestations. Nevertheless, clinical and animal experiments have allowed a comprehensive understanding of the mechanisms underlying CPSP occurrence, based on which different theoretical hypotheses have been proposed. We reviewed and collected the literature and on the mechanisms of CPSP by searching the English literature in PubMed and EMBASE databases for the period 2002–2022. Recent studies have reported that CPSP occurrence is mainly due to post-stroke nerve injury and microglial activation, with an inflammatory response leading to central sensitization and de-inhibition. In addition to the primary injury at the stroke site, peripheral nerves, spinal cord, and brain regions outside the stroke site are involved in the occurrence and development of CPSP. In the present study, we reviewed the mechanism of action of CPSP from both clinical studies and basic research based on its sensory pathway. Through this review, we hope to increase the understanding of the mechanism of CPSP.

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The Calcium Channel α2δ1 Subunit: Interactional Targets in Primary Sensory Neurons and Role in Neuropathic Pain

Cited by 20 publications

References 108 publications

WITHDRAWN: The Molecular Signature Associated with Oxaliplatin Induced Peripheral Neuropathy in Colorectal Cancer

WITHDRAWN: The Molecular Signature Associated with Oxaliplatin Induced Peripheral Neuropathy in Colorectal Cancer

Exploring the mechanism of immediate analgesic effect of 1-time tuina intervention in minor chronic constriction injury rats using RNA-seq

Role of Sensory Pathway Injury in Central Post-Stroke Pain: A Narrative Review of Its Pathogenetic Mechanism

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