Role of 1 ‐Deoxysphingolipids in docetaxel neurotoxicity

AbstractA major dose ‐limiting side effect of docetaxel chemotherapy is peripheral neuropathy. Patients’ symptoms include pain, numbness, tingling and burning sensations, and motor weakness in the extremities. The molecular mechanism is currently not understood, and there are no treatments available. Previously, we have shown an association between neuropathy symptoms of patients treated with paclitaxel and the plasma levels of neurotoxic sphingolipids, the 1‐deoxysphingolipids (1‐deoxySL) (Kramer et al, FASEB J, 2015). 1‐deoxySL are produced when the first enzyme of the sphingolipid biosynthetic pathway , serine palmitoyltransferase (SPT), uses L‐alanine as a substrate instead of its canonical amino acid substrate, L‐serine. In the current investigation, we tested whether 1‐deoxySL accumulate in the nervous system following systemic docetaxel treatment in mice. In dorsal root ganglia (DRG), w e observed that docetaxel (45 mg/kg cumulative dose) significantly elevated the levels of 1‐deoxySL and L‐serine‐derived ceramides, but not sphingosine‐1‐phosphate (S1P). S1P is a bioactive sphingolipid and a ligand for specific G‐protein coupled receptors. In the sciatic nerve, docetaxe l decreased 1‐deoxySL and ceramides. Moreover, we show that in primary DRG cultures, 1‐deoxysphingosine produced neurite swellings that could be reversed with S1P. Our results demonstrate that docetaxel chemotherapy up‐regulates sphingolipid metabolism in sensory ne...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research

Related Links:

This study provides evidence that neuroendocrine stress axis activity has a marked, sexually dimorphic, effect on paclitaxel-induced painful CIPN.
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
This article summarizes the FDA review and the data supporting the approval of ado-trastuzumab emtansine as a component of treatment for patients with HER2-positive EBC with residual disease. PMID: 32217612 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Conditions:   Chemotherapy-induced Peripheral Neuropathy;   Pain, Neuropathic;   Pain Syndrome Interventions:   Drug: Ozone;   Drug: Oxygen Sponsors:   Bernardino Clavo, MD, PhD;   Servicio Canario de Salud;   Instituto de Salud Carlos III;   Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC);   Fundación DISA, Spain;   Fundación Española del Dolor (FED) Not yet recruiting
Source: - Category: Research Source Type: clinical trials
asu Neuropathic pain is a common symptom and is associated with an impaired quality of life. It is caused by the lesion or disease of the somatosensory system. Neuropathic pain syndromes can be subdivided into two categories: central and peripheral neuropathic pain. The present review highlights the peripheral neuropathic models, including spared nerve injury, spinal nerve ligation, partial sciatic nerve injury, diabetes-induced neuropathy, chemotherapy-induced neuropathy, chronic constriction injury, and related conditions. The drugs which are currently used to attenuate peripheral neuropathy, such as antidepressants,...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
This study was designed to observe the effects of Corydalis saxicola Bunting total alkaloids (CSBTA) on cisplatin-induced neuropathic pain and to explore its potential mechanisms. In this study, the rats received intraperitoneal injection of 2mg/kg cisplatin twice a week for five weeks. Meanwhile, oral administration of low (30mg/kg)-, medium (60mg/kg)- and high (120mg/kg)-dose CSBTA were given daily for five weeks. By using Von-frey hair, heat radiant and -80∘C cold acetone, we found that CSBTA could obviously relieve cisplatin-induced mechanical, heat, and cold hyperalgesia. It has been verified that cisplatin-induced ...
Source: The American Journal of Chinese Medicine - Category: Complementary Medicine Authors: Tags: Am J Chin Med Source Type: research
Authors: Kachrani R, Santana A, Rogala B, Pawasauskas J Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a chronic symptom associated with chemotherapy treatment. Symptoms and severity vary based on chemotherapeutic agent used and dose. At present, effective options for the prevention and treatment of CIPN are inadequate and clinical guidance is limited. Unknown mechanism of action, lack of efficacy in many traditional neuropathic pain medications, and inconsistent evidence in regard to drug therapy have further complicated evaluation of therapeutic options. Twenty-five studies were identified and eval...
Source: Journal of Pain and Palliative Care Pharmacotherapy - Category: Palliative Care Tags: J Pain Palliat Care Pharmacother Source Type: research
ConclusionsDiminished peripheral BDNF resources and Met-BDNF-SNP genotype are associated with augmented symptoms of PN in patients with type II diabetes mellitus. Sensitivity thresholds to hot pain signals may be less influenced by depression and possibly more accurately detect PN symptoms in diabetic patients.
Source: Acta Diabetologica - Category: Endocrinology Source Type: research
Deepti Ahuja, Sachidanand Jee Bharati, Nishkarsh Gupta, Vinod Kumar, Sushma BhatnagarIndian Journal of Cancer 2020 57(1):93-97 Scrambler therapy (ST) is a novel noninvasive modality for treatment of chronic neuropathic and cancer pain using 5 artificial neurons. The principle with Scrambler Therapy is that synthetic “non-pain” information is transmitted by C fiber surface receptors. Chemotherapy-induced peripheral neuropathy can markedly deteriorate patient's quality of life and can also negatively affect compliance with the anticancer treatment. Chronic neuropathic pain presents a therapeutic challenge if...
Source: Indian Journal of Cancer - Category: Cancer & Oncology Authors: Source Type: research
No abstract available
Source: Topics in Pain Management - Category: Anesthesiology Tags: ARTICLE Source Type: research
ConclusionThis is an initial report demonstrating the potential of rTMS for the treatment of CIPN. We suggest rTMS could be potentially beneficial and effective as a treatment for pain and dysesthesia in patients with CIPN.
Source: Journal of Clinical Neuroscience - Category: Neuroscience Source Type: research
More News: Brain | Chemotherapy | Docetaxel | Neurology | Neuroscience | Pain | Peripheral Neuropathy | Taxotere