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It frequently arises as a consequence of damage to first-order nociceptive neurons in the lumbar dorsal root ganglia (DRG), with chromatolysis being the primary neuropathological response following sciatic nerve injury (SNI). Nevertheless, the function of miRNAs in modulating this chromatolytic response in the context of neuropathic pain remains unexplored. Our previous research demonstrated that the intracisternal administration of a miR-30c mimic accelerates the development of neuropathic pain, whereas the inhibition of miR-30c prevents pain onset and reverses established allodynia. In the present study, we sought to elucidate the role of miR-30c-5p in the pathogenesis of neuropathic pain, with a particular focus on its impact on DRG neurons following SNI. The organisation and ultrastructural changes in DRG neurons, particularly in the protein synthesis machinery, nucleolus, and Cajal bodies (CBs), were analysed. The results demonstrated that the administration of a miR-30c-5p mimic exacerbates chromatolytic damage and nucleolar stress and induces CB depletion in DRG neurons following SNI, whereas the administration of a miR-30c-5p inhibitor alleviates these effects. We proposed that three essential cellular responses\u2014nucleolar stress, CB depletion, and chromatolysis\u2014are the pathological mechanisms in stressed DRG neurons underlying neuropathic pain. Moreover, miR-30c-5p inhibition has a neuroprotective effect by reducing the stress response in DRG neurons, which supports its potential as a therapeutic target for neuropathic pain management. This study emphasises the importance of miR-30c-5p in neuropathic pain pathogenesis and supports further exploration of miRNA-based treatments.<\/jats:p>","DOI":"10.3390\/ijms252111427","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T05:47:33Z","timestamp":1729748853000},"page":"11427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["miR-30c-5p Gain and Loss of Function Modulate Sciatic Nerve Injury-Induced Nucleolar Stress Response in Dorsal Root Ganglia Neurons"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-4852","authenticated-orcid":false,"given":"Raquel","family":"Franc\u00e9s","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Instituto Marqu\u00e9s de Valdecilla (IDIVAL), 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5726-8814","authenticated-orcid":false,"given":"Jorge","family":"Mata-Garrido","sequence":"additional","affiliation":[{"name":"Instituto Marqu\u00e9s de Valdecilla (IDIVAL), 39011 Santander, Spain"},{"name":"Departamento de Anatom\u00eda y Biolog\u00eda Celular, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3402-1152","authenticated-orcid":false,"given":"Miguel","family":"Lafarga","sequence":"additional","affiliation":[{"name":"Instituto Marqu\u00e9s de Valdecilla (IDIVAL), 39011 Santander, Spain"},{"name":"Departamento de Anatom\u00eda y Biolog\u00eda Celular, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7710-1358","authenticated-orcid":false,"given":"Mar\u00eda A.","family":"Hurl\u00e9","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Instituto Marqu\u00e9s de Valdecilla (IDIVAL), 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2447-8928","authenticated-orcid":false,"given":"M\u00f3nica","family":"Tramullas","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Facultad de Medicina, Universidad de Cantabria, 39011 Santander, Spain"},{"name":"Instituto Marqu\u00e9s de Valdecilla (IDIVAL), 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1097\/j.pain.0000000000001939","article-title":"The revised International Association for the Study of Pain definition of pain: Concepts, challenges, and compromises","volume":"161","author":"Raja","year":"2020","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/S0140-6736(21)00393-7","article-title":"Chronic pain: An update on burden, best practices, and new advances","volume":"397","author":"Cohen","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.pain.2013.11.013","article-title":"Neuropathic pain in the general population: A systematic review of epidemiological studies","volume":"155","author":"Austin","year":"2014","journal-title":"Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.neurol.2018.09.016","article-title":"Neuropathic pain: Definition, assessment and epidemiology","volume":"175","author":"Bouhassira","year":"2019","journal-title":"Rev. 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