Notch activation enhances microglial CX3CR1/P38 MAPK pathway in rats model of vincristine-induced peripheral neuropathy

Publication date: Available online 11 November 2019Source: Neuroscience LettersAuthor(s): Bingjie Qin, Yuxing Li, Xiaohu Liu, Denghui Gong, Weihong ZhengAbstarctChemotherapy-induced peripheral neuropathy (CIPN) has a adverse impact to the living quality of cancer patients. This side effect of CIPN limit the dose of drug used in many chemotherapies, such as vincristine (VCR). The activation of microglia in the spinal dorsal horn is involved in the occurrence and development of neuropathic pain induced by VCR. Recent study has demonstrated that hypoxia induced microglia activation depends on Notch signaling, and it is involved in the release of many inflammatory related factors in microglia. In this work, we aimed to study that the role of Notch signaling pathway in microglia activation on a VCR-induced neuropathy rat model. Our results showed that the mechanical, thermal and cold pain threshold of rats was decreased by treatment of VCR, but N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor, relieved the hyperalgesia. Molecular analysis showed that activation of Notch signaling pathway increased after nerve injury and that DAPT could signifcantly inhibit the upregulation of Notch signaling pathway, the activation of microglia, and the release of pro-inflammatory cytokines in the spinal. Taking together, Notch signaling pathway could be a potential therapeutic target to alleviate neuropathic pain.
Source: Neuroscience Letters - Category: Neuroscience Source Type: research

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In conclusion, our findings indicate that early exposure to regional hypothermia alleviates paclitaxel-induced peripheral neuropathy. Therapeutic hypothermia may therefore represent an economical and nonpharmaceutical preventive strategy for CIPN in patients with localized solid tumors.
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
​BY JENNIFER TUONG; IVAN KHARCHENKO; JEAN LUC AGARD; &AHMED RAZIUDDIN, MDA 65-year-old man who had HIV well-controlled with highly active antiretroviral therapy, hypertension, sciatica, and restless leg syndrome presented to the emergency department with left leg pain. He also had had chemotherapy and radiation for anal cancer. The patient said the pain had started 45 minutes earlier when he was sitting on the toilet.He described the pain as sore in quality and 10/10 on the pain scale. He reported that it had started in his lower back and radiated to his left leg. He said he had had no trauma or weakness to the regio...
Source: The Case Files - Category: Emergency Medicine Tags: Blog Posts Source Type: research
to JB Abstract Painful peripheral neuropathy is the most dose-limiting side effect of paclitaxel (PTX), a widely used anti-cancer drug to treat solid tumours. The understanding of the mechanisms involved in this side effect is crucial to the development of new therapeutic approaches. CXCL1 chemokine and its receptor CXCR2 have been pointed as promising targets to treat chronic pain. Herein, we sought to evaluate the possible involvement of CXCL1 and CXCR2 in the pathogenesis of PTX-induced neuropathic pain in mice. PTX treatment led to increased levels of CXCL1 in both dorsal root ganglion and spinal cord samples....
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research
This study not only provides biological evidence to support the use of duloxetine as the first standard CIPN drug but will also lead to potential new targets for CIPN drug development. Introduction A major dose-limiting complication of chemotherapy is chemotherapy-induced peripheral neuropathy (CIPN). The greatest contributors to CIPN are taxanes (e.g., paclitaxel) and platinum-based (e.g., oxaliplatin) treatments (Krukowski et al., 2015). Paclitaxel (PTX) can effectively treat several of the most common cancers including breast cancer, lung cancer, and ovarian cancer (Ewertz et al., 2015; Cetinkaya-Fisgin et al., ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
DISCUSSION:: We observed no difference between sham and real ST CIPN treatment. Potential reasons include at least the following: ST does not work; the sham treatment had some effect; small sample size with heterogeneous patients; misplaced electrodes on an area of nonpainful but damaged nerves; or a combination of these factors. PMID: 30714486 [PubMed - as supplied by publisher]
Source: Journal of Palliative Care - Category: Palliative Care Tags: J Palliat Care Source Type: research
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Source: Journal of Neurochemistry - Category: Neurology Authors: Tags: Original Article Source Type: research
This study evaluated the validity and reliability of a Chinese version of the Neuropathic Pain Symptom Inventory (C-NPSI) in patients with colorectal cancer and chemotherapy-induced peripheral neuropathy.MethodsThis cross-sectional study recruited 106 patients from a cancer center in Northern Taiwan. The C-NPSI was obtained through the translation and back-translation of the original NPSI. Content validity was evaluated by 10 experts. Internal consistency reliability was assessed through Pearson correlation analysis. Construct validity was conducted by confirmed factor analysis. Convergent validity was examined using the C...
Source: Journal of the Formosan Medical Association - Category: General Medicine Source Type: research
Conclusions: The data for the first time revealed specific signaling pathways leading to BTZ-induced peripheral neuropathic pain, including the activation of mTOR and PI3K. Inhibition of these signal pathways alleviates pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of peripheral painful neuropathy observed during chemotherapeutic application of BTZ.Cell Physiol Biochem 2018;48:54 –62
Source: Cellular Physiology and Biochemistry - Category: Cytology Source Type: research
by Drew RosielleWe have a'required reading'list for our fellowship, which includes a bunch of what I think are landmark or otherwise really important studies. One of them is thisvery well done RCT of continuous ketamine infusions for patients with cancer pain, which showed it to be ineffective (and toxic).We also recently have seen another high-quality study published with negative results for ketamine. This was a Scottish, multi-center, randomized, placebo-controlled, intention-to-treat, and double-blinded study oforal ketamine for neuropathic pain in cancer patients. The study involved 214 patients, 75% of whom were thro...
Source: Pallimed: A Hospice and Palliative Medicine Blog - Category: Palliative Care Tags: fatigue ketamine methylphenidate neuropathic pain research research issues rosielle The profession Source Type: blogs
Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of cancer treatment that significantly compromises quality of life of cancer patients and survivors. Identification of targets for pharmacological intervention to prevent or reverse CIPN is needed. We investigated exchange protein regulated by cAMP (Epac) as a potential target. Epacs are cAMP-binding proteins known to play a pivotal role in mechanical allodynia induced by nerve injury and inflammation. We demonstrate that global Epac1-knockout (Epac1−/−) male and female mice are protected against paclitaxel-induced mechanical allodynia. In...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
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