Cell-specific role of histone deacetylase 6 in chemotherapy-induced mechanical allodynia and loss of intraepidermal nerve fibers

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side effect of cancer treatment with no Food and Drug Administration-approved medication for its prevention or management. Using RNA sequencing analysis of dorsal root ganglia (DRG), we identify critical contributions of histone deacetylase 6 (HDAC6) and mitochondrial damage to the establishment of CIPN in a mouse model of cisplatin-induced neuropathy. We show that pharmacological inhibition of HDAC6 using ACY-1215 or global deletion of HDAC6 is sufficient to prevent cisplatin-induced mechanical allodynia, loss of intraepidermal nerve fibers (IENFs), and mitochondrial bioenergetic deficits in DRG neurons and peripheral nerves in male and female mice. The bioenergetic deficits in the neuronal cell bodies in the DRG are characterized by reduced oxidative phosphorylation, whereas the mitochondrial deficits in the nerves are due to a reduction in axonal mitochondrial content. Notably, deleting HDAC6 in sensory neurons protects against the cisplatin-induced loss of IENFs and the reduction in mitochondrial bioenergetics and content in the peripheral nerve. By contrast, deletion of HDAC6 in sensory neurons only partially and transiently prevents cisplatin-induced mechanical allodynia and does not protect against impairment of mitochondrial function in DRG neurons. We further reveal a critical role of T cells in the protective effects of HDAC6 inhibition on these signs of CIPN. In summary, we show that cisplatin-i...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

Related Links:

CONCLUSIONS: Both topical and systemic gabapentin exhibit a propensity to attenuate CIPN in a cisplatin paradigm. Gabapentin applied topically may therefore provide an adjunctive or alternative route for CIPN management upon cessation of systemic medications due to intolerable side-effects. PMID: 31462283 [PubMed - in process]
Source: BMC Pharmacology and Toxicology - Category: Drugs & Pharmacology Tags: BMC Pharmacol Toxicol 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
AbstractIncreases in cancer diagnosis have tremendous negative impacts on patients and their families, and major societal and economic costs. The beneficial effect of chemotherapeutic agents on tumor suppression comes with major unwanted side effects such as weight and hair loss, nausea and vomiting, and neuropathic pain. Chemotherapy-induced peripheral neuropathy (CIPN), which can include both painful and non-painful symptoms, can persist 6  months or longer after the patient’s last chemotherapeutic treatment. These peripheral sensory and motor deficits are poorly treated by our current analgesics with limited ...
Source: Drugs - Category: Drugs & Pharmacology Source Type: research
Recent albeit limited evidence suggests that body mass index (BMI) may be a modifiable risk factor to reduce the deleterious effects of chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors.
Source: Journal of Pain and Symptom Management - Category: Palliative Care Authors: 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
This is a rare study to investigate the relationship among daily activity, mood, and quality of life (QoL) in colorectal cancer patients with chemotherapy ‐induced peripheral neuropathy (CIPN), by using the mediation effect analysis. According to the results, the mediation effect of mood between daily activities and QoL should be further emphasized for colorectal cancer patients with CIPN. AbstractChemotherapy ‐induced peripheral neuropathy (CIPN) with restriction of daily activity (RDA) was common consequence of oxaliplatin‐based chemotherapy in colorectal cancer patients. CIPN with RDA and negative mood may impact ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Chemotherapy-induced peripheral neuropathy (CIPN) and neurologic pain in cancer patients are manifestations that impact patient quality of life both during and after treatment. Management of CIPN and pain requires pharmacogenetic knowledge of genes such as CYP2D6 that play a major role in drug metabolism. CYP2D6 ’s varying levels of drug metabolic activity have been correlated with specific functional polymorphisms. In this pilot study, a novel multiplex single-nucleotide polymorphism (SNP) extension panel analyzing SNPs within CYP2D6 was evaluated for clinical relevance in identifying patients at risk fo r developin...
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: 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
Abstract Neuropathic cancer pain (NCP) is caused by nerve damage attributable to the cancer per se, and/or treatments including chemotherapy, radiotherapy, and surgery; the prevalence is reported to be as high as 40%. The etiologies of NCP include direct nerve invasion or nerve compression by the cancer, neural toxicity, chemotherapy, and radiotherapy. NCP is subdivided into plexopathy, radiculopathy, and peripheral neuropathies, among several other categories. The clinical characteristics of NCP differ from those of nociceptive pain in terms of both the hypersensitivity symptoms (burning, tingling, and an electri...
Source: The Korean Journal of Internal Medicine - Category: Internal Medicine Authors: Tags: Korean J Intern Med Source Type: research
Abstract Purpose The Society for Integrative Oncology (SIO) produced an evidence-based guideline on use of integrative therapies during and after breast cancer treatment that was determined to be relevant to the American Society of Clinical Oncology (ASCO) membership. ASCO considered the guideline for endorsement. Methods The SIO guideline addressed the use of integrative therapies for the management of symptoms and adverse effects, such as anxiety and stress, mood disorders, fatigue, quality of life, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep ...
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: J Clin Oncol Source Type: research
More News: Anesthesiology | Brain | Cancer | Cancer & Oncology | Chemotherapy | Food and Drug Administration (FDA) | Neurology | Pain | Pain Management | Peripheral Neuropathy