Lidocaine for Oxaliplatin-induced Neuropathy
Ontology highlight
ABSTRACT:
DISEASE(S): Neuropathy, Painful,Chemotherapy-induced Peripheral Neuropathy,Pain,Peripheral Nervous System Diseases,Neuropathic Pain,Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2252152 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Chemotherapy induced peripheral neuropathy (CIPN) is a dose-limiting painful neuropathy that occurs commonly during cancer management, which often leads to the discontinuation of medication. Previous studies suggest that the α9α10 nicotinic acetylcholine receptor (nAChR) specific antagonist αO-conotoxin GeXIVA[1,2] is effective in CIPN models, however the related mechanisms remains unclear. Here we analyzed the preventive effect of GeXIVA[1,2] on neuropathic pain in the long-term oxaliplatin injection induced CIPN model. At the end of treatment, lumbar (L4-L6) spinal cord was extracted, and RNA-sequencing and bioinformatic analysis were performed to investigate the potential genes and pathways related to CIPN and GeXIVA[1,2]. GeXIVA[1,2] inhibited the development of mechanical allodynia induced by chronic oxaliplatin treatment. Repeated injections of GeXIVA[1,2] for 3 weeks have no effect on mice normal pain threshold or locomotor activity and anxiety-like behavior as evaluated in the open field test (OFT) and elevated plus maze (EPM). Our RNA-sequencing results identified 209 differentially expressed genes (DEGs) in CIPN model, simultaneously injection of GeXIVA[1,2] with oxaliplatin altered 53 of the identified DEGs. These reverted genes were significantly enriched in immune-related pathways represented by cytokine-cytokine receptor interaction pathway. Our findings suggest that GeXIVA[1,2] could be a potential therapeutic compound for chronic oxaliplatin induced CIPN management.
2024-01-18 | GSE253183 | GEO
Project description:Vincristine, oxaliplatin, and cisplatin are commonly prescribed chemotherapeutic agents for the treatment of several cancer types. However, a main side-effect is chemotherapy-induced peripheral neuropathy (CIPN), which may lead to decreased quality of life, changes in chemotherapeutic treatment or even treatment cessation. Although painful symptoms associated with CIPN are faithfully recapitulated by mouse models, there is limited knowledge of how these drugs affect the expression of genes in peripheral sensory neurons. The present study carried out a transcriptomic analysis of dorsal root ganglia isolated from mice treated with vincristine, oxaliplatin, and cisplatin with a view to gain insight into the comparative pathophysiological mechanisms of CIPN. RNA-Seq using 75-nucleotide single end runs revealed 368, 295 and 256 differential expressed genes (DEGs) induced by treatment with vincristine, oxaliplatin and cisplatin, respectively. Although there were many similarities in DEGs between chemotherapeutic agents, only 5 genes were dysregulated in all groups. Cell type enrichment analysis (CTEA) and gene set enrichment analysis (GSEA) showed predominant effects on genes associated with the immune system after treatment with vincristine, while oxaliplatin treatment affected mainly neuronal genes. Treatment with cisplatin resulted in a mixed inflammatory and neuropathic gene expression signature. Only ‘regulation of transport’ and ‘response to external stimuli’ were gene ontology terms shared between all treatments. These results provide insight into the recruitment of innate and adaptive immune responses to DRG tissue and indicate enhanced neuro-inflammatory processes following administration of vincristine, oxaliplatin, and cisplatin. These gene expression signatures may provide insight into novel drug targets for treatment of CIPN.
2019-06-01 | GSE125001 | GEO
Project description:Vincristine, oxaliplatin, and cisplatin are commonly prescribed chemotherapeutic agents for the treatment of several cancer types. However, a main side-effect is chemotherapy-induced peripheral neuropathy (CIPN), which may lead to decreased quality of life, changes in chemotherapeutic treatment or even treatment cessation. Although painful symptoms associated with CIPN are faithfully recapitulated by mouse models, there is limited knowledge of how these drugs affect the expression of genes in peripheral sensory neurons. The present study carried out a transcriptomic analysis of dorsal root ganglia isolated from mice treated with vincristine, oxaliplatin, and cisplatin with a view to gain insight into the comparative pathophysiological mechanisms of CIPN. RNA-Seq using 75-nucleotide single end runs revealed 368, 295 and 256 differential expressed genes (DEGs) induced by treatment with vincristine, oxaliplatin and cisplatin, respectively. Although there were many similarities in DEGs between chemotherapeutic agents, only 5 genes were dysregulated in all groups. Cell type enrichment analysis (CTEA) and gene set enrichment analysis (GSEA) showed predominant effects on genes associated with the immune system after treatment with vincristine, while oxaliplatin treatment affected mainly neuronal genes. Treatment with cisplatin resulted in a mixed inflammatory and neuropathic gene expression signature. Only ‘regulation of transport’ and ‘response to external stimuli’ were gene ontology terms shared between all treatments. These results provide insight into the recruitment of innate and adaptive immune responses to DRG tissue and indicate enhanced neuro-inflammatory processes following administration of vincristine, oxaliplatin, and cisplatin. These gene expression signatures may provide insight into novel drug targets for treatment of CIPN.
2019-06-01 | GSE125002 | GEO
Project description:This study aimed to explore the possible mechanism of lidocaine-induced neurotoxicity. A total of 40 rats were randomly assigned to 4 groups (n = 10 per group): control group; sham group, received only intrathecal catheter insertion; saline group, received an intrathecal injection of saline; and lidocaine group, received an intrathecal injection of 10% lidocaine. Neurobehavioral tests were performed on rats in each group before injection and 1, 2, 3, and 4 days after the intrathecal injection. On the fourth day, after completing neurobehavioral tests, the spinal cords of all rats from L2 to L6 were removed and immediately stored in liquid nitrogen. In the control and lidocaine groups, parts of the spinal cord tissues of three rats were selected for gene microarray analysis.Based on the results of the gene chip analysis,Five rats in each group underwent real-time quantitative polymerase chain reaction (PCR) and five Western blot analysis to verify Differentially expressed genes at the mRNA transcription and protein levels. The aim of gene chip analysis is to screen potential genes involved in lidocaine-induced neurotoxicity.
2019-09-05 | GSE136833 | GEO
Project description:Primary objectives: ?To establish the efficacy of E-52862 to reduce the incidence and the severity of OXL-induced chronic neuropathy in patients treated for colorectal cancer.?To explore the efficacy of E-52862 to reduce the severity and duration of OXL-induced acute neuropathy.?To evaluate whether E-52862 can raise the cumulative total dose of OXL than can be delivered without dose-limiting chronic neuropathy.?To explore the incidence of dose-reduction, dose-delays and discontinuation of oxaliplatin due to symptomatic neuropathy grade 3 or 4.?To explore the incidence of adverse events by severity, of serious adverse events, of adverse events leading to E 52862 discontinuation and of adverse events related to E-52862 by severity.?To assess E-52862 plasma exposure associated with the treatment.
Primary endpoints: Efficacy endpoints:-Evolution of the clinical Total Neuropathy Score (cTNS).-Change from baseline of the reduced Total Neuropathy Score (rTNS).-Evolution of cold-induced pain intensity.-Change from baseline of the number and duration of signs and symptoms of OXL-induced acute neuropathy assessed with the specific OXL-induced neuropathy questionnaire.-Level of peripheral sensory neuropathy toxicity at each visit assessed with the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria.-Time to the first occurrence of NCI-CTCAE grade 2, 3 or 4 symptomatic neuropathy.-Change from baseline of the amplitudes of sensory and motor nerve action potentials and of the sensitive and motor nerve conduction velocities measured in the nerve conduction tests.-Evolution of patients’s quality of life assessed with the Quality of Life Questionnaire C30 (QLQ-C30) with the module for chemotherapy-induced neuropathy (QLQ-CIPN20).-Proportion of patients who meet any of the following definitions of neuropathy at the end of the study: a) at least subclinical neuropathy: cTNS >2, b) manifest neuropathy: rTNS > or equal 5, c) symptomatic neuropathy: grade >1 NCI-CTCAE toxicity, and d) severe neuropathy: grade > or =3 NCI-CTCAE toxicity.-Incidence of dose-reduction, dose-delays and discontinuation of oxaliplatin due to symptomatic neuropathy grade 3 or 4.-Total cumulative dose of OXL administered.
Safety endpoitns:-Incidence of adverse events by severity, of serious adverse events, of adverse events leading to E-52862 discontinuation and of adverse events related to E-52862 by severity. Values for these variables will be obtained in all visits of the study, except in the screening visit.-E-52862 plasma concentration associated with the treatment.
| 2530562 | ecrin-mdr-crc
Project description:Gene expression signatures of chemotherapy-induced neuropathy induced by cisplatin and oxaliplatin
| PRJNA514863 | ENA
Project description:Oxaliplatin-induced chronic peripheral neuropathy is of major concern to oncologists and patients as it has been shown to affect patients’ health-related quality of life. Although a number of interventions have been implicated, none of them can be recommended for clinical use. This therapeutic failure reflects a poor understanding of the real mechanism of oxaliplatin-induced neuropathy. However, oxidative stress is identified to be one of the main biomolecular dysfunctions in this neuropathy. Rood’s approach is a neurophysiological approach that is based on reflexes of the central nervous system in which the sensory stimulation provides desired muscular response and was specially designed for patients with motor control problems. It was developed by Margeret Rood in 1940. According to Rood, sensory stimulation can activate or deactivate the receptor by facilitation or inhibition, which makes it possible to get the desired muscular response.
| 61819 | ecrin-mdr-crc
Project description:Oxaliplatin is a chemotherapeutic agent, which is generally used in treatment of colorectal cancer. The dose limiting side effect of oxaliplatin is neurotoxicity. In this study we aimed to determine whether glutamine has role in prevention of oxaliplatin induced neuropathy.
| 2157857 | ecrin-mdr-crc
Project description:Gene expression signatures of chemotherapy-induced neuropathy induced by vincristine, cisplatin and oxaliplatin
| PRJNA514860 | ENA
Project description:We use back skin of WT SD rats, or imiquimod(IMQ)-induced psoraisis-like rat model treated with or without epidural injection of 1% lidocaine. We isolate total RNA for RNA-sequencing.
2020-03-13 | GSE146891 | GEO