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

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This study was a pilot randomized controlled trial, which was conducted with cooperation between Beijing University of Chinese Medicine (BUCM), China, and Tehran University of Medical Science (TUMS), Iran. Forty participants with CIPN were randomly assigned (1 : 1) to receive twelve sessions of acupuncture (20 minutes each session over 4 weeks) or take one 300 mg tablet of vitamin B1 and three 300 mg capsules of gabapentin per day for 4 weeks, after which both groups were followed up for 4 weeks. The primary endpoint was CIPN symptom severity measured by the Numerical Rating Scale (NRS). The sec...
Source: Pain Research and Management - Category: Anesthesiology Authors: Tags: Pain Res Manag Source Type: research
This is a review of the evidence from studies of the efficacy and tolerability of topically applied, high-concentration (8%) capsaicin in Chemotherapy-induced peripheral neuropathy (CIPN). Methods: For this review, we searched EMBASE and MEDLINE to 14 April 2020. The terms used in the search included capsaicin patch, chemotherapy-induced peripheral neuropathy, cancer pain or malignant pain. Results: A total of 69 studies were obtained but only 5 were selected for the final analysis. Capsaicin 8% patch provides significant pain relief in CIPN, and may lead to regeneration and restoration of sensory nerve fibers.
Source: Journal of Pain and Symptom Management - Category: Palliative Care Authors: 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
dante Most patients with multiple myeloma (MM) suffer from chronic pain at every stage of the natural disease process. This review focuses on the most common causes of chronic pain in MM patients: (1) pain from myeloma bone disease (MBD); (2) chemotherapy-induced peripheral neuropathy as a possible consequence of proteasome inhibitor therapy (i.e., bortezomib-induced); (3) post-herpetic neuralgia as a possible complication of varicella zoster virus reactivation because of post-transplantation immunodepression; and (4) pain in cancer survivors, with increasing numbers due to the success of antiblastic treatments, which ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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
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