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Mitochondria AND pain

Alejandro Vicente-Carrillo
In vitro drug-induced toxicity assessment demands the usability and validation of suitable cell models, obtained non-invasively and pain-free. Sperm suspensions, painlessly and easily obtained from breeding boars, have been proven as suitable biosensors for pre-clinical toxicology screening and ranking of lead compounds in the drug development processes on a kinematics-based assay. Having a limited number of mitochondria and depending on these mitochondria and on cytoplasmic glycolysis for the energy needed for motility and for plasma membrane functionality, spermatozoa become a suitable model for capturing multiple modes of action of drugs and other chemicals acting via measurements of sperm motility...
March 2, 2018: Basic & Clinical Pharmacology & Toxicology
Yohei Tatematsu, Haruhi Fujita, Hiroki Hayashi, Atsushi Yamamoto, Atsushi Tabata, Hideaki Nagamune, Kazuto Ohkura
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammation and pain. In the present study, we examined the effects of celecoxib, a cyclooxygenase-2 (COX-2)-selective NSAID, on rat liver mitochondrial function. Celecoxib dose-dependently induced mitochondria swelling, which was not suppressed by cyclosporine A (CsA). The oxygen consumption rate in mitochondria-suspended solution was facilitated by the addition of celecoxib, and its uncoupling activity was observed. Celecoxib also suppressed SF6847-induced uncoupling, and appeared to exert inhibitory effects on the electron transport chain...
2018: Biological & Pharmaceutical Bulletin
Marija Sajic, Keila Kazue Ida, Ryan Canning, Norman A Gregson, Michael R Duchen, Kenneth J Smith
BACKGROUND: Small-diameter, myelinated axons are selectively susceptible to dysfunction in several inflammatory PNS and CNS diseases, resulting in pain and degeneration, but the mechanism is not known. METHODS: We used in vivo confocal microscopy to compare the effects of inflammation in experimental autoimmune neuritis (EAN), a model of Guillain-Barré syndrome (GBS), on mitochondrial function and transport in large- and small-diameter axons. We have compared mitochondrial function and transport in vivo in (i) healthy axons, (ii) axons affected by experimental autoimmune neuritis, and (iii) axons in which mitochondria were focally damaged by laser induced photo-toxicity...
February 27, 2018: Journal of Neuroinflammation
Derrick Lonsdale
Starting with a brief history of beriberi and the discovery that thiamin deficiency is its cause, the symptoms and signs are reviewed. None are pathognomonic. The disease has a low mortality and a long morbidity. The appearance of the patient can be deceptive, often being mistaken for psychosomatic disease in the early stages. The chemistry of thiamin and the laboratory methodology for depicting its deficiency are outlined. The diseases associated with thiamin deficiency, apart from malnutrition, include a number of genetically determined conditions where mutations, either in the cofactor relationship or a transporter, provide the etiology...
2018: Advances in Food and Nutrition Research
Jiacheng Ma, Annemieke Kavelaars, Patrick M Dougherty, Cobi J Heijnen
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side effect of many chemotherapeutic agents, affecting >60% of patients with cancer. Moreover, CIPN persists long into survivorship in approximately 20% to 30% of these patients. To the authors' knowledge, no drugs have been approved to date by the US Food and Drug Administration to effectively manage chemotherapy-induced neuropathic pain. The majority of the drugs tested for the management of CIPN aim at symptom relief, including pain and paresthesia, yet are not very efficacious...
February 20, 2018: Cancer
Hanneke L D M Willemen, Annemieke Kavelaars, Judith Prado, Mirjam Maas, Sabine Versteeg, Lara J J Nellissen, Jeshua Tromp, Rafael Gonzalez Cano, Wenjun Zhou, Magnus E Jakobsson, Jędrzej Małecki, George Posthuma, Abdella M Habib, Cobi J Heijnen, Pål Ø Falnes, Niels Eijkelkamp
Chronic pain is a debilitating problem, and insights in the neurobiology of chronic pain are needed for the development of novel pain therapies. A genome-wide association study implicated the 5p15.2 region in chronic widespread pain. This region includes the coding region for FAM173B, a functionally uncharacterized protein. We demonstrate here that FAM173B is a mitochondrial lysine methyltransferase that promotes chronic pain. Knockdown and sensory neuron overexpression strategies showed that FAM173B is involved in persistent inflammatory and neuropathic pain via a pathway dependent on its methyltransferase activity...
February 14, 2018: PLoS Biology
S Zanella, F Buccelletti, F Franceschi, A Vassiliadis, C Ramponi, S Sivolella, A Zanoni, F Lumachi
OBJECTIVE: Long-term physical inactivity can cause the atrophy of skeletal muscle. The aim of this study is to explore the underlying mechanisms of physical inactivity-induced atrophy of skeletal muscle. MATERIALS AND METHODS: 14 Sprague- Dawley (SD) male rats were divided into 2 groups including normal control (NC) and hindlimb suspension (HS) groups. After two weeks of HS stimulation, the ratio between skeletal muscle weight and body weight, and cross-sectional area (CSA) of skeletal muscle fibers, were measured...
January 2018: European Review for Medical and Pharmacological Sciences
Mohammad Waseem, Pooja Kaushik, Heena Tabassum, Suhel Parvez
BACKGROUND: Even though chemotherapeutic regimens shows considerable importance, it may cause progressive, continuing and sometimes irreversible peripheral neuropathy. Chemotherapy induced peripheral neuropathy (CIPN) comprises of sensory abnormalities that are most distress issues. The mechanism associated with CIPN pathogenesis is not completely revealed and is treatment is still questionable. The purpose of this review was to investigate the role of mitochondria in CIPN. METHODS: This review is literature based that describes the mitochondrial mechanism underlying CIPN and the neuropathic complications associated with different antineoplastic agents...
December 7, 2017: Current Drug Metabolism
Lawrence Van Helleputte, Mandy Kater, Dana P Cook, Caroline Eykens, Elisabeth Rossaert, Wanda Haeck, Tom Jaspers, Natasja Geens, Pieter Vanden Berghe, Conny Gysemans, Chantal Mathieu, Wim Robberecht, Philip Van Damme, Guido Cavaletti, Matthew Jarpe, Ludo Van Den Bosch
As cancer is becoming more and more a chronic disease, a large proportion of patients is confronted with devastating side effects of certain anti-cancer drugs. The most common neurological complications are painful peripheral neuropathies. Chemotherapeutics that interfere with microtubules, including plant-derived vinca-alkaloids such as vincristine, can cause these chemotherapy-induced peripheral neuropathies (CIPN). Available treatments focus on symptom alleviation and pain reduction rather than prevention of the neuropathy...
March 2018: Neurobiology of Disease
Hyun Yi, Shue Liu, Yuta Kashiwagi, Daigo Ikegami, Wan Huang, Hirotsugu Kanda, Takafumi Iida, Ching-Hang Liu, Keiya Takahashi, David A Lubarsky, Shuanglin Hao
Chronic pain is increasingly recognized as an important comorbidity of HIV-infected patients, however, the exact molecular mechanisms of HIV-related pain are still elusive. CCAAT/enhancer binding proteins (C/EBPs) are expressed in various tissues, including the CNS. C/EBPβ, one of the C/EBPs, is involved in the progression of HIV/AIDS, but the exact role of C/EBPβ and its upstream factors are not clear in HIV pain state. Here, we used a neuropathic pain model of perineural HIV envelope glycoprotein gp120 application onto the rat sciatic nerve to test the role of phosphorylated C/EBPβ (pC/EBPβ) and its upstream pathway in the spinal cord dorsal horn (SCDH)...
January 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Chih-Hsiung Hsieh, Chueh-Hsuan Lu, Wei-Ting Chen, Bo-Lun Ma, Chih-Yu Chao
Traditional therapies for pancreatic cancer are usually expensive and likely to cause side effects, and most patients have the risk of recurrence and suffering pain. Here, we investigated combination treatment of epigallocatechin-3-gallate (EGCG) and non-invasive low strength pulsed electric field (PEF) on the human pancreatic cell line PANC-1. Cells were cultured in various concentrations of EGCG and exposed to trains of PEF. The results showed that the low strength PEF alone or single treatment with low concentration of EGCG did not obviously affect the cell proliferation and migration in PANC-1...
2017: PloS One
Michael R Hamblin
Photobiomodulation (PBM) involves the use of red or near-infrared light at low power densities to produce a beneficial effect on cells or tissues. PBM therapy is used to reduce pain, inflammation, edema, and to regenerate damaged tissues such as wounds, bones, and tendons. The primary site of light absorption in mammalian cells has been identified as the mitochondria and, more specifically, cytochrome c oxidase (CCO). It is hypothesized that inhibitory nitric oxide can be dissociated from CCO, thus restoring electron transport and increasing mitochondrial membrane potential...
November 22, 2017: Photochemistry and Photobiology
Agostinho G Rocha, Simon A B Knight, Alok Pandey, Heeyong Yoon, Jayashree Pain, Debkumar Pain, Andrew Dancis
Fe-S clusters are cofactors that participate in diverse and essential biological processes. Mitochondria contain a complete machinery for Fe-S cluster assembly. Cysteine desulfurase (Nfs1) is required generation of a form of activated sulfur and is essential for the initial Fe-S cluster assembly step. Using mass-spectometry we identified proteins that were copurified with Nfs1 using a pull-down strategy, including a novel protein kinase. Furthermore, we were able to identify phosphorylation sites on the Nfs1 protein...
December 2017: Data in Brief
Kuan-Hung Chen, Chien-Hui Yang, Christopher Glenn Wallace, Chung-Ren Lin, Chia-Kai Liu, Tsung-Cheng Yin, Tien-Hung Huang, Yi-Ling Chen, Cheuk-Kwan Sun, Hon-Kan Yip
This study tested the hypothesis that combination therapy using extracorporeal shock wave (ECSW)-melatonin (Mel) was superior to either alone at ameliorating neuropathic pain (NP). NP was induced by chronic constriction injury (CCI) to the left sciatic nerve in rats. Animals were categorized into sham control (group 1), CCI only (group 2), CCI-ECSW (group 3), CCI-Mel (group 4) and CCI-ECSW-Mel (group 5). By days 2 and 8 after CCI, the mechanical paw withdrawal threshold (MPWT)/thermal paw withdrawal latency (TPWL) were highest in group 2, lowest in group 1, significantly lower in group 5 than in groups 3 and 4 (all p<0...
2017: American Journal of Translational Research
S Jampa-Ngern, K Viravaidya-Pasuwat, S Suvanasuthi, A Khantachawana
Low level laser therapy is widely used to relieve pain and inflammation, and to restore cellular functions. The photons of light are absorbed by mitochondria in cells, leading to an increase in the production of adenosine triphosphate (ATP), nitric oxide release, blood flow, and reactive oxygen species (ROS). This study proposed the use of a laser diode array at 808 nm to stimulate the proliferation and to activate the functions of dermal papilla cells, which were an important part of the hair growth cycle...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Agostinho G Rocha, Simon A B Knight, Alok Pandey, Heeyong Yoon, Jayashree Pain, Debkumar Pain, Andrew Dancis
The cysteine desulfurase Nfs1/Isd11 uses the amino acid cysteine as the substrate and its activity is absolutely required for contributing persulfide sulfur to the essential process of iron-sulfur (Fe-S) cluster assembly in mitochondria. Here we describe a novel regulatory process involving phosphorylation of Nfs1 in mitochondria. Phosphorylation enhanced cysteine desulfurase activity, while dephosphorylation decreased its activity. Nfs1 phosphopeptides were identified, and the corresponding phosphosite mutants showed impaired persulfide formation...
September 21, 2017: Mitochondrion
Helen F Galley, Barry McCormick, Kirsten L Wilson, Damon A Lowes, Lesley Colvin, Carole Torsney
Chemotherapy-induced neuropathic pain is a debilitating and common side effect of cancer treatment. Mitochondrial dysfunction associated with oxidative stress in peripheral nerves has been implicated in the underlying mechanism. We investigated the potential of melatonin, a potent antioxidant that preferentially acts within mitochondria, to reduce mitochondrial damage and neuropathic pain resulting from the chemotherapeutic drug paclitaxel. In vitro, paclitaxel caused a 50% reduction in mitochondrial membrane potential and metabolic rate, independent of concentration (20-100 μmol/L)...
November 2017: Journal of Pineal Research
Michael R Hamblin
Photobiomodulation (PBM) also known as low-level level laser therapy is the use of red and near-infrared light to stimulate healing, relieve pain, and reduce inflammation. The primary chromophores have been identified as cytochrome c oxidase in mitochondria, and calcium ion channels (possibly mediated by light absorption by opsins). Secondary effects of photon absorption include increases in ATP, a brief burst of reactive oxygen species, an increase in nitric oxide, and modulation of calcium levels. Tertiary effects include activation of a wide range of transcription factors leading to improved cell survival, increased proliferation and migration, and new protein synthesis...
2017: AIMS Biophysics
V N Perfilova, T A Popova, I I Prokofiev, I S Mokrousov, O V Ostrovskii, I N Tyurenkov
Increased oxygen consumption by heart and brain mitochondria in the absence of ADP and reduced mitochondrial respiration in the presence of ADP were observed in rats exposed to stress simulated by suspension by the dorsal neck skin fold for 24 h, which attests to uncoupling of substrate oxidation and ATP synthesis and can cause electron drain from the respiratory chain, formation of ROS, and oxidative damage to cell structures. Blockade of inducible NO synthase with aminoguanidine (single intraperitoneal dose of 50 mg/kg before stress exposure) increased coupling of respiration and oxidative phosphorylation in heart and brain mitochondria of rats exposed to immobilization-painful stress, which was especially pronounced in cardiomyocytes...
June 2017: Bulletin of Experimental Biology and Medicine
Min Jia, Caihua Wu, Fang Gao, Hongchun Xiang, Ning Sun, Ping Peng, Jingjing Li, Xiaocui Yuan, Hongping Li, Xianfang Meng, Bo Tian, Jing Shi, Man Li
Background Paclitaxel is commonly used as a cancer chemotherapy drug that frequently causes peripheral neuropathic pain. Inflammasome is a multiprotein complex consisting of Nod-like receptor proteins (NLRPs), apoptosis-associated speck-like protein, and caspase-1, which functions to switch on the inflammatory process and the release of interleukin-1β. Growing evidences have supported that peripheral interleukin-1β is critical in enhancing paclitaxel-induced neuropathic pain. However, whether activation of NLRP3 inflammasome in peripheral nerve contributes to paclitaxel-induced neuropathic pain is still unclear...
January 2017: Molecular Pain
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