Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic pain
Diabetic neuropathic pain (DNP) is one of the most prevalent complications of diabetes, characterized by a high global prevalence and a substantial affected population with limited effective therapeutic options. Although DNP is closely associated with hyperglycemia, an increasing body of research su...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1480534/full |
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| author | Jie Wu Jie Wu Haijun Hu Haijun Hu Xi Li Xi Li |
| author_facet | Jie Wu Jie Wu Haijun Hu Haijun Hu Xi Li Xi Li |
| author_sort | Jie Wu |
| collection | DOAJ |
| description | Diabetic neuropathic pain (DNP) is one of the most prevalent complications of diabetes, characterized by a high global prevalence and a substantial affected population with limited effective therapeutic options. Although DNP is closely associated with hyperglycemia, an increasing body of research suggests that elevated blood glucose levels are not the sole inducers of DNP. The pathogenesis of DNP is intricate, involving the release of inflammatory mediators, alterations in synaptic plasticity, demyelination of nerve fibers, and ectopic impulse generation, yet the precise mechanisms remain to be elucidated. The spinal dorsal horn coordinates dynamic interactions between peripheral and central pain pathways, wherein dorsal horn neurons, microglia, and astrocytes synergize with Schwann cell-derived signals to process nociceptive information flow. Abnormally activated neurons can alter signal transduction by modifying the local microenvironment, compromising myelin integrity, and diminishing trophic support, leading to neuronal sensitization and an amplifying effect on peripheral pain signals, which in turn triggers neuropathic pain. Ion channels play a pivotal role in signal conduction, with the modulation of sodium, potassium, and calcium channels being particularly crucial for the regulation of pain signals. In light of the rising incidence of diabetes and the current scarcity of effective DNP treatments, a thorough investigation into the interactions between neurons and glial cells, especially the mechanisms of ion channel function in DNP, is imperative for identifying potential drug targets, developing novel therapeutic strategies, and thereby enhancing the prospects for DNP management. |
| format | Article |
| id | doaj-art-de17d181303c4c76af3d368b0cb7e4fe |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-de17d181303c4c76af3d368b0cb7e4fe2025-08-20T02:16:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.14805341480534Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic painJie Wu0Jie Wu1Haijun Hu2Haijun Hu3Xi Li4Xi Li5Department of Anesthesiology, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaKey Laboratory of Anesthesiology of Jiangxi Province, Nanchang, Jiangxi, ChinaDepartment of Anesthesiology, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaKey Laboratory of Anesthesiology of Jiangxi Province, Nanchang, Jiangxi, ChinaDepartment of Anesthesiology, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, ChinaKey Laboratory of Anesthesiology of Jiangxi Province, Nanchang, Jiangxi, ChinaDiabetic neuropathic pain (DNP) is one of the most prevalent complications of diabetes, characterized by a high global prevalence and a substantial affected population with limited effective therapeutic options. Although DNP is closely associated with hyperglycemia, an increasing body of research suggests that elevated blood glucose levels are not the sole inducers of DNP. The pathogenesis of DNP is intricate, involving the release of inflammatory mediators, alterations in synaptic plasticity, demyelination of nerve fibers, and ectopic impulse generation, yet the precise mechanisms remain to be elucidated. The spinal dorsal horn coordinates dynamic interactions between peripheral and central pain pathways, wherein dorsal horn neurons, microglia, and astrocytes synergize with Schwann cell-derived signals to process nociceptive information flow. Abnormally activated neurons can alter signal transduction by modifying the local microenvironment, compromising myelin integrity, and diminishing trophic support, leading to neuronal sensitization and an amplifying effect on peripheral pain signals, which in turn triggers neuropathic pain. Ion channels play a pivotal role in signal conduction, with the modulation of sodium, potassium, and calcium channels being particularly crucial for the regulation of pain signals. In light of the rising incidence of diabetes and the current scarcity of effective DNP treatments, a thorough investigation into the interactions between neurons and glial cells, especially the mechanisms of ion channel function in DNP, is imperative for identifying potential drug targets, developing novel therapeutic strategies, and thereby enhancing the prospects for DNP management.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1480534/fulldiabetic neuropathic painmicrogliaastrocytesSchwann cellsion channelsspinal dorsal horn |
| spellingShingle | Jie Wu Jie Wu Haijun Hu Haijun Hu Xi Li Xi Li Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic pain Frontiers in Immunology diabetic neuropathic pain microglia astrocytes Schwann cells ion channels spinal dorsal horn |
| title | Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic pain |
| title_full | Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic pain |
| title_fullStr | Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic pain |
| title_full_unstemmed | Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic pain |
| title_short | Spinal neuron-glial crosstalk and ion channel dysregulation in diabetic neuropathic pain |
| title_sort | spinal neuron glial crosstalk and ion channel dysregulation in diabetic neuropathic pain |
| topic | diabetic neuropathic pain microglia astrocytes Schwann cells ion channels spinal dorsal horn |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1480534/full |
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