Neuroprotective effect of angiotensin II type 2 receptor stimulation in vincristine-induced mechanical allodynia

Peripheral neuropathy is the major dose-limiting side effect of many currently used chemotherapies, such as vincristine (VCR). We recently demonstrated that candesartan, an angiotensin II type 1 receptor antagonist, was neuroprotective against resiniferatoxin-induced sensory neuropathy, and that this effect is mediated by stimulation of the angiotensin II type 2 receptor (AT2R). Thus, we evaluated the effect of preventive treatment with candesartan and a specific AT2R agonist, C21, on a mouse model of VCR-induced neuropathy. Vincristine was administered daily for 7 days to male Swiss mice. Treatment with candesartan and C21 was started on day 1, before VCR treatment, and continued until day 7. We evaluated the development of VCR-induced neuropathy and the effect of treatment by functional tests, immunohistochemical analyses of intraepidermal nerve fibers and dorsal root ganglia neurons, and ultrastructural analysis of the sciatic nerve. Mice treated with VCR showed high mechanical allodynia but no modifications of motor performance or mechanical/thermal nociception. Treatment with candesartan and C21 completely restored normal tactile sensitivity of VCR-treated mice. Both drugs prevented VCR-induced nonpeptidergic intraepidermal nerve fiber loss. Only C21 displayed neuroprotective effects against VCR-induced loss and enlargement of myelinated nerve fibers in the sciatic nerve. Our finding that candesartan and C21 are protective against VCR-induced neuropathic pain through AT2...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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AbstractPurposeCIPN is a common, debilitating, and dose-limiting side effect of chemotherapy. Here, we describe characteristics of patients with CIPN using both patient-reported outcomes (PRO) and quantitative sensory testing (QST).MethodsBreast cancer survivors with persistent moderate to severe CIPN defined by a rating of 4 or greater on a 0 –10 Numeric Rating Scale (NRS) from two ongoing clinical trials were included. PROs included the Neuropathic Pain Scale (NPS) and Functional Assessment of Cancer Therapy-Gynecologic Oncology Group/Neurotoxicity (FACT/GOG-Ntx). QST included tactile and vibration detection thresh...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
In this study, we assessed losartan ’s analgesic effect on paclitaxel-induced neuropathic pain (PINP) in rats and its mechanism of action in dorsal root ganglion (DRG). Rats received intraperitoneal injections of 2 mg/kg paclitaxel on days 0, 2, 4, and 6 and received single or multiple intraperitoneal injections of losartan potassi um dissolved in phosphate-buffered saline at various times. The mechanical thresholds, protein levels of inflammatory cytokines, and cellular location of AT1R and interleukin 1β (IL-1β) in the DRG were assessed with behavioral testing, Western blotting, and immunohistochemis...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
Conditions:   Chemotherapy-Induced Peripheral Neuropathy;   Malignant Neoplasm Interventions:   Other: Quality-of-Life Assessment;   Other: Questionnaire Administration;   Procedure: Transcranial Direct Current Stimulation Sponsors:   M.D. Anderson Cancer Center;   National Cancer Institute (NCI) Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
CONCLUSION: Women with CIPN after adjuvant taxane therapy for breast cancer experienced significant improvements in neuropathic symptoms from an 8-week acupuncture treatment regimen. Additional larger studies are needed to confirm these findings. IMPLICATIONS FOR PRACTICE: Chemotherapy-induced peripheral neuropathy (CIPN) is a toxicity that often persists for months to years after the completion of adjuvant chemotherapy for early breast cancer. In a randomized pilot trial of 40 breast cancer survivors with CIPN, an 8-week acupuncture intervention (vs. usual care) led to a statistically and clinically significant impro...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
by Drew Rosielle (@drosielle)A Series of Observations on Opioids By a Palliative Doc Who Prescribes A Lot of Opioids But Also Has Questions.This is the 5th post in a series about opioids, with a focus on how my thinking about opioids has changed over the years. See also:Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid DosesPart 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Ano...
Source: Pallimed: A Hospice and Palliative Medicine Blog - Category: Palliative Care Tags: cancer opioids pain rosielle The profession Source Type: blogs
Pharmacological interventions targeting Wnt/β-catenin signaling pathway attenuate paclitaxel-induced peripheral neuropathy. Eur J Pharmacol. 2019 Oct 03;:172714 Authors: Resham K, Sharma SS Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling pain condition which occurs as a consequence of cancer chemotherapy with anti-cancer agents like paclitaxel, oxaliplatin, etc. Despite immense research in the pathological pathways involved in CIPN, treatment options still remain limited. Recently, pathological involvement of Wnt signaling has been investigated in various neuropathic pai...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
Chemotherapy-induced peripheral neuropathy syndrome causes significant pain in hands and feet and is an adverse effect of treatment. This is the first study to explore a somatic yoga and meditation intervention on functional outcomes and quality of life.
Source: Archives of Physical Medicine and Rehabilitation - Category: Rehabilitation Authors: Source Type: research
This article synthesizes the literature on efficacy and tolerability of extremity cryotherapy during taxane administration to identify if it is an intervention that can be provided to patients to mitigate these symptoms. METHODS: A literature review was performed using PubMed®, the Cochrane Database of Systematic Reviews, Ovid, Web of Science, and CINAHL®. 46 articles were initially identified, and 10 articles were reviewed (5 related to nail changes and 5 related to neuropathy). FINDINGS: Larger, powered studies are needed on these topics; however, existing data suggest this intervention as a promising l...
Source: Clinical Journal of Oncology Nursing - Category: Nursing Authors: Tags: Clin J Oncol Nurs Source Type: research
AbstractPurposeWhile older adults with cancer are more likely to develop chemotherapy-induced peripheral neuropathy (CIPN), the study aimed to determine if patient-reported and objective measures of CIPN differ by age among cancer survivors.MethodsCancer survivors with persistent CIPN after completion of platinum and/or taxane chemotherapy completed CIPN questionnaires (severity, interference with activities, sensory, and motor symptoms) and objective testing (light touch, vibration, pain, cold sensation). CIPN measures were compared by age group (
Source: Supportive Care in Cancer - Category: Cancer & Oncology Source Type: research
(Natural News) Researchers recently found a connection between local acupuncture points and the peripheral nerves involved in neuropathy and neuropathic pain. They concluded that stimulating those local points with needles ensures the successful treatment of peripheral neuropathy. Numerous studies show that acupuncture improves medical conditions like chronic lower back pain, migraine and tension headaches, and chemotherapy-related...
Source: NaturalNews.com - Category: Consumer Health News Source Type: news
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