Paclitaxel-induced painful neuropathy is associated with changes in mitochondrial bioenergetics, glycolysis, and an energy deficit in dorsal root ganglia neurons

Abstract: Painful neuropathy is the major dose-limiting side effect of paclitaxel chemotherapy. Mitochondrial dysfunction and adenosine triphosphate (ATP) deficit have previously been shown in peripheral nerves of paclitaxel-treated rats, but the effects of paclitaxel in the dorsal root ganglia (DRGs) have not been explored. The aim of this study was to determine the bioenergetic status of DRG neurons following paclitaxel exposure in vitro and in vivo. Utilising isolated DRG neurons, we measured respiratory function under basal conditions and at maximal capacity, glycolytic function, and Adenosine diphosphate (ADP)/ATP levels at 3 key behavioural timepoints; prior to pain onset (day 7), peak pain severity and pain resolution. At day 7, maximal respiration and spare reserve capacity were significantly decreased in DRG neurons from paclitaxel-treated rats. This was accompanied by decreased basal ATP levels and unaltered ADP levels. At peak pain severity, respiratory function was unaltered, yet glycolytic function was significantly increased. Reduced ATP and unaltered ADP levels were also observed at the peak pain timepoint. All these effects in DRG neurons had dissipated by the pain resolution timepoint. None of these paclitaxel-evoked changes could be replicated from in vitro paclitaxel exposure to naive DRG neurons, demonstrating the impact of in vivo exposure and the importance of in vivo models. These data demonstrate the nature of mitochondrial dysfunction evoked by in viv...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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Publication date: 19 November 2019Source: Cell Reports, Volume 29, Issue 8Author(s): Hao Luo, Hui-Zhu Liu, Wen-Wen Zhang, Megumi Matsuda, Ning Lv, Gang Chen, Zhen-Zhong Xu, Yu-Qiu ZhangSummaryThe proinflammatory cytokine interleukin-17 (IL-17) is implicated in pain regulation. However, the synaptic mechanisms by which IL-17 regulates pain transmission are unknown. Here, we report that glia-produced IL-17 suppresses inhibitory synaptic transmission in the spinal cord pain circuit and drives chemotherapy-induced neuropathic pain. We find that IL-17 not only enhances excitatory postsynaptic currents (EPSCs) but also suppresse...
Source: Cell Reports - Category: Cytology Source Type: research
Authors: Fukuda H, Takekuma M, Hirashima Y Abstract A 62-year-old Japanese woman developed numbness of the extremities and megaloblastic anemia. She had undergone total abdominal hysterectomy, whole-pelvis radiation therapy and chemotherapy for gynecological cancer 10 years before. Chronic abdominal pain, diarrhea and intermittent small-bowel obstruction had afflicted her for a long time. We diagnosed her with vitamin B12 deficiency anemia and polyneuropathy due to chronic radiation enteritis causing malabsorption. Vitamin B12 injections improved her numbness and anemia. The early diagnosis and treatment of deficie...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
Publication date: Available online 19 November 2019Source: Materials Science and Engineering: CAuthor(s): Bing Liang, Deyu Zuo, Kexiao Yu, Xiaojun Cai, Bin Qiao, Rui Deng, Junsong Yang, Lei Chu, Zhongliang Deng, Yuanyi Zheng, Guoqing ZuoAbstractMyelosuppression, gastrointestinal toxicity and hypersensitivities always accompany chemotherapy of osteosarcoma (OS). In addition, the intricate karyotype of OS, the lack of targeted antitumor drugs and the bone microenvironment that provides a protective alcove for tumor cells reduce the therapeutic efficacy of chemotherapy. Here, we developed a multifunctional bone cement loaded ...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research
Authors: Van Slambrouck J, Vlasselaers J, Devos B Abstract Peritoneal tuberculosis is a rare extrapulmonary manifestation of tuberculosis. Considering the diagnosis of peritoneal tuberculosis in a low prevalence setting can be vital for the further clinical management in selected patients.In a young male with migration background, presenting with generalised abdominal pain, computed tomography revealed ascites, omental and peritoneal thickening and enlarged mesentery lymph nodes. Computed tomography also revealed a distal ureteral calculus at the right vesico-ureteral junction. Diagnostic laparoscopy showed a nodul...
Source: Acta Chirurgica Belgica - Category: Surgery Tags: Acta Chir Belg Source Type: research
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), an...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
ConclusionThis preliminary study demonstrated PG2 injection exhibited an excellent safety profile, and has potential in ameliorating the deterioration in QoL and the AEs associated with active anticancer treatment among patients with advanced pharyngeal or laryngeal HNSCC under CCRT. Further research in patients with other cancer types or treatment modalities may widen PG2 ’s application in clinical settings.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
Authors: Morris AL, Colbourne T, Kirkpatrick I, Banerji V Abstract Nontraumatic chylous pleural effusions (chylothorax) and pericardial effusions (chylopericardium) are rare. They can, however, accompany intrathoracic malignancies and, most commonly, lymphomas. An association of chronic lymphocytic leukemia (cll) with chylopericardium has rarely been reported. A 68-year-old woman with cll, previously treated with single-agent fludarabine in the community, developed pleuritic chest pain and a new pericardial effusion. Computed tomography (ct) imaging of her chest revealed a large pericardial effusion with progressiv...
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
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Source: Prostaglandins and Other Lipid Mediators - Category: Lipidology Source Type: research
Conclusions: We found that the addition of a regional anesthesia fellow to the APS team was not associated with statistically significant differences in total opioid consumption or hospital length of stay in this surgical population. The addition of trainees to the infrastructure, with vigilant supervision, is not associated with change in outcomes. PMID: 31684716 [PubMed - as supplied by publisher]
Source: Korean Journal of Anesthesiology - Category: Anesthesiology Tags: Korean J Anesthesiol Source Type: research
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Source: Journal of Pain and Symptom Management - Category: Palliative Care Authors: Tags: Original Article Source Type: research
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