Targeting glial cells as a therapeutic approach for the treatment of chemotherapy-induced neuropathic pain
Chemotherapy-induced peripheral neuropathy (CIPN) is the most common adverse effect of many first-line antineoplastic agents, which negatively affects the quality of life and clinical outcome. Current clinical management of this condition provides unsatisfactory efficacy and unwanted side effects, h...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/673349 |
| Acceso en línea: | http://hdl.handle.net/10803/673349 |
| Access Level: | acceso abierto |
| Palabra clave: | Neuropathic pain Chemotherapy Glial cells Transcriptomics Sigma-1 receptor Dolor neuropático Quimioterapia Células gliales Transcriptómica Receptor Sigma-1 616 |
| Sumario: | Chemotherapy-induced peripheral neuropathy (CIPN) is the most common adverse effect of many first-line antineoplastic agents, which negatively affects the quality of life and clinical outcome. Current clinical management of this condition provides unsatisfactory efficacy and unwanted side effects, highlighting the urgent need for the identification and development of novel effective therapeutic strategies that can prevent or mitigate this debilitating disease. Accumulating evidence has revealed that glial cells are powerful contributors to pathological pain of different etiologies; however, relatively little is known about their role in CIPN. In the present Thesis we have first characterized the involvement of glial cells, especially astrocytes, in the pathophysiology of CIPN by using a mouse model of vincristine-induced neuropathic pain together with a cellspecific transcriptomic approach. Bioinformatic analysis revealed predominant effects on genes associated with important astrocyte homeostatic functions after vincristine treatment, producing a strong downregulation indicating widespread astrocyte dysfunction. Alternatively, we have demonstrated the analgesic efficacy of a novel compound antagonist of sigma-1 receptors (σ1R) on this disease model and described its modulatory role in astrocytes. Overall, we provided unique insights to advance in the understanding of the complexity of CIPN and identified astrocytes as potential therapeutic targets for better management of this pathology. |
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