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Drug induced peripheral neuropathy

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https://www.readbyqxmd.com/read/28323403/discovery-of-potent-antiallodynic-agents-for-neuropathic-pain-targeting-p2x3-receptors
#1
Young-Hwan Jung, Yong-Chul Kim, Yeo Ok Kim, Hai Lin, Joong-Heui Cho, Jin-Hee Park, So-Deok Lee, Jinsu Bae, Koon Mook Kang, Yoon Gyoon Kim, Ae Nim Pae, Hyojin Ko, Chul-Seung Park, Myung Ha Yoon
Antagonism of the P2X3 receptor is one of the potential therapeutic strategies for the management of neuropathic pain because P2X3 receptors are predominantly localized on small to medium diameter C- and Aδ-fiber primary afferent neurons, which are related to the pain-sensing system. In this study, 5-hydroxy pyridine derivatives were designed, synthesized, and evaluated for their in vitro biological activities by two-electrode voltage clamp assay at hP2X3 receptors. Among the novel hP2X3 receptor antagonists, intrathecal treatment of compound 29 showed parallel efficacy with pregabalin (calcium channel modulator) and higher efficacy than AF353 (P2X3 receptor antagonist) in the evaluation of its antiallodynic effects in spinal nerve ligation rats...
March 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28317148/bortezomib-induced-peripheral-neuropathy-a-genome-wide-association-study-on-multiple-myeloma-patients
#2
Chiara Campo, Miguel Inacio da Silva Filho, Niels Weinhold, Seyed Hamidreza Mahmoudpour, Hartmut Goldschmidt, Kari Hemminki, Maximilian Merz, Asta Försti
The proteasome-inhibitor bortezomib was introduced into the treatment of multiple myeloma more than a decade ago. It is clinically beneficial, but peripheral neuropathy (PNP) is a side effect that may limit its use in some patients. To examine the possible genetic predisposing factors to PNP, we performed a genome-wide association study on 646 bortezomib-treated German multiple myeloma patients. Our aim was to identify genetic risk variants associated with the development of PNP as a serious side effect of the treatment...
March 20, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28315678/protective-effect-of-co-administration-of-curcumin-and-sildenafil-in-alcohol-induced-neuropathy-in-rats
#3
Maninder Kaur, Amarjeet Singh, Bimlesh Kumar, Sachin Kumar Singh, Amit Bhatia, Monica Gulati, T Prakash, Palak Bawa, Adil Hussain Malik
Neuropathic pain associated with chronic alcohol consumption is a medico-socioeconomical problem that affects both central and peripheral nervous system and has no satisfactory treatment till date. The present study was designed to investigate the protective effect of co-administration of curcumin and sildenafil on alcohol induced neuropathic pain in rats. In order to carry out this, ethanol (35% v/v, 10g/kg, p.o.) was administered for 10 weeks to induce neuropathic pain. Curcumin (30 and 60mg/kg, i.p.) and sildenafil (5 and 10mg/kg, i...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28299349/gabapentin-inhibits-protein-kinase-c-epsilon-translocation-in-cultured-sensory-neurons-with-additive-effects-when-coapplied-with-paracetamol-acetaminophen
#4
Vittorio Vellani, Chiara Giacomoni
Gabapentin is a well-established anticonvulsant drug which is also effective for the treatment of neuropathic pain. Although the exact mechanism leading to relief of allodynia and hyperalgesia caused by neuropathy is not known, the blocking effect of gabapentin on voltage-dependent calcium channels has been proposed to be involved. In order to further evaluate its analgesic mechanisms, we tested the efficacy of gabapentin on protein kinase C epsilon (PKCε) translocation in cultured peripheral neurons isolated from rat dorsal root ganglia (DRGs)...
2017: TheScientificWorldJournal
https://www.readbyqxmd.com/read/28286483/long-term-effects-pathophysiological-mechanisms-and-risk-factors-of-chemotherapy-induced-peripheral-neuropathies-a-comprehensive-literature-review
#5
REVIEW
Nicolas Kerckhove, Aurore Collin, Sakahlé Condé, Carine Chaleteix, Denis Pezet, David Balayssac
Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28286117/carvedilol-prevents-functional-deficits-in-peripheral-nerve-mitochondria-of-rats-with-oxaliplatin-evoked-painful-peripheral-neuropathy
#6
Aparna Areti, Prashanth Komirishetty, Ashutosh Kumar
Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a)...
March 9, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28271282/characterization-of-the-peripheral-neuropathy-associated-with-brentuximab-vedotin-treatment-of-mycosis-fungoides-and-s%C3%A3-zary-syndrome
#7
Zachary A Corbin, Annie Nguyen-Lin, Shufeng Li, Ziba Rahbar, Mahkam Tavallaee, Hannes Vogel, Katrin A Salva, Gary S Wood, Youn H Kim, Seema Nagpal
Chemotherapy-induced peripheral neuropathy (CIPN) is common, frequently limits chemotherapy dosing, and negatively impacts quality of life. The National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0, and the Total Neuropathy Score clinical version (TNSc) are both validated scores to quantify peripheral neuropathy (PN), with the TNSc being more sensitive to clinical changes. Mycosis fungoides and Sézary syndrome (MF/SS) are characterized by a chronic course, where current therapies are generally non-curative and treatment toxicities have the potential for significant lasting effects...
March 7, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28237807/effects-of-paclitaxel-on-the-development-of-neuropathy-and-affective-behaviors-in-the-mouse
#8
Wisam Toma, S Lauren Kyte, Deniz Bagdas, Yasmin Alkhlaif, Shakir D Alsharari, Aron H Lichtman, Zhi-Jian Chen, Egidio Del Fabbro, John W Bigbee, David A Gewirtz, M Imad Damaj
Paclitaxel, one of the most commonly used cancer chemotherapeutic drugs, effectively extends the progression-free survival of breast, lung, and ovarian cancer patients. However, paclitaxel and other chemotherapy drugs elicit peripheral nerve fiber dysfunction or degeneration that leads to peripheral neuropathy in a large proportion of cancer patients. Patients receiving chemotherapy also often experience changes in mood, including anxiety and depression. These somatic and affective disorders represent major dose-limiting side effects of chemotherapy...
February 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28204996/incidence-of-taxane-induced-peripheral-neuropathy-receiving-treatment-and-prescription-patterns-in-patients-with-breast-cancer
#9
Su Jeong Song, Ji Min, Sung Yun Suh, Sun Hoi Jung, Hyeon Joo Hahn, Seock-Ah Im, Ju-Yeun Lee
PURPOSE: Taxane-induced peripheral neuropathy (TIPN) can affect quality of life and treatment outcomes in breast cancer patients. Despite the high incidence, treatment of PN has not been established. This study aimed to evaluate the incidence, risk factors, and prescribing pattern of TIPN receiving pharmacologic treatment in real-world practice. METHODS: We conducted a retrospective chart review of 1629 breast cancer patients who received taxanes at the Seoul National University Hospital from July 2012 to June 2014...
February 16, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28194306/a-randomized-exploratory-phase-2-study-in-patients-with-chemotherapy-related-peripheral-neuropathy-evaluating-whole-body-vibration-training-as-adjunct-to-an-integrated-program-including-massage-passive-mobilization-and-physical-exercises
#10
Stefan S Schönsteiner, Heidi Bauder Mißbach, Axel Benner, Silja Mack, Thomas Hamel, Michael Orth, Bernhard Landwehrmeyer, Sigurd D Süßmuth, Carolin Geitner, Regine Mayer-Steinacker, Anneliese Riester, Andrea Prokein, Elfriede Erhardt, Jelena Kunecki, Anna M Eisenschink, Rainer Rawer, Hartmut Döhner, Elisabeth Kirchner, Richard F Schlenk
BACKGROUND: Chemotherapy-induced polyneuropathy (CIPN) is a common toxicity after chemotherapy, immunomodulatory drugs or proteasome inhibitors, which is difficult to treat and may also have impact on quality of life. The objective of the study was to evaluate whole-body vibration (WBV) on the background of an integrated program (IP) including massage, passive mobilization and physical exercises on CIPN. PATIENTS AND METHODS: In an exploratory phase-2 study patients with CIPN (NCI CTC grade 2/3) were randomized for WBV plus IP (experimental) to IP alone (standard)...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28186109/astragali-radix-could-it-be-an-adjuvant-for-oxaliplatin-induced-neuropathy
#11
Lorenzo Di Cesare Mannelli, Alessandra Pacini, Laura Micheli, Angelo Pietro Femia, Mario Maresca, Matteo Zanardelli, Alfredo Vannacci, Eugenia Gallo, Anna Rita Bilia, Giovanna Caderni, Fabio Firenzuoli, Alessandro Mugelli, Carla Ghelardini
Neurotoxicity is a major side effect of platinum derivatives both during and after treatment. In the absence of effective pharmacological compounds, the opportunity to identify safe adjuvant treatments among medicinal plants seems appropriate. Astragali radix is an adaptogenic herbal product recently analyzed in platinum-treated cancer patients. With the aim of evaluating the anti-neuropathic profile of Astragali radix, a previously characterized aqueous (Aqu) and two hydroalcoholic (20%HA and 50%HA) extracts were tested in a rat model of oxaliplatin-induced neuropathy...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28182729/rikkunshito-prevents-paclitaxel-induced-peripheral-neuropathy-through-the-suppression-of-the-nuclear-factor-kappa-b-nf%C3%AE%C2%BAb-phosphorylation-in-spinal-cord-of-mice
#12
Junzo Kamei, Shunsuke Hayashi, Akane Sakai, Yuki Nakanishi, Misa Kai, Megumi Ikegami, Hiroko Ikeda
Peripheral neuropathy is the major side effect caused by paclitaxel, a microtubule-binding antineoplastic drug. Paclitaxel-induced peripheral neuropathy causes a long-term negative impact on the patient's quality of life. However, the mechanism underlying paclitaxel-induced peripheral neuropathy is still unknown, and there is no established treatment. Ghrelin is known to attenuate thermal hyperalgesia and mechanical allodynia in chronic constriction injury of the sciatic nerve, and inhibit the activation of nuclear factor kappa B (NFκB) in the spinal dorsal horn...
2017: PloS One
https://www.readbyqxmd.com/read/28156448/effectiveness-of-massage-therapy-mt-as-a-treatment-strategy-and-preventive-modality-for-chemotherapy-induced-peripheral-neuropathy-cipn-symptoms
#13
Regina Cobb, Alejandro Ramon Carvajal, Kathi Healey, Diane D'Ambra, N Joseph Espat
193 Background: CIPN has a known negative impact on quality of life (QoL) and can be a dose-limiting side effect of cytotoxic drugs with no generally agreed upon therapeutic intervention. In this study MT was assessed as a primary and secondary preventive modality of CIPN symptoms under the hypothesis that it can be used as an effective prophylactic and therapeutic option. METHODS: A single arm 10-week prospective study (n = 62) with pre/post intervention assessment using a validated survey instrument adapted from "Peripheral neuropathy associated with novel therapies […]"...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28119076/spinal-astrocytic-c-jun-n-terminal-kinase-jnk-activation-as-counteracting-mechanism-to-the-amitriptyline-analgesic-efficacy-in-painful-peripheral-neuropathies
#14
Maria Domenica Sanna, Carla Ghelardini, Nicoletta Galeotti
Several drugs and agents are currently used for the treatment of neuropathic pain. Among them amitriptyline, a tricyclic antidepressant drug, represent a first line treatment. Despite its well-documented clinical efficacy, amitriptyline is ineffective in some animal models of neuropathic pain. The aim of this study was to investigate into amitriptyline poor efficacy in neuropathic pain and to determine the role of c-Jun N-terminal kinase (JNK) activation as counteracting mechanism to the analgesic effects of this drug...
January 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28115644/multiparametric-image-analysis-of-rat-dorsal-root-ganglion-cultures-to-evaluate-peripheral-neuropathy-inducing-chemotherapeutics
#15
Liang Guo, John Hamre, Sandy Eldridge, Holger P Behrsing, Facundo M Cutuli, Jodie Mussio, Myrtle Davis
Chemotherapy-induced peripheral neuropathy (CIPN) is a major, dose-limiting adverse effect experienced by cancer patients. Advancements in mechanism-based risk mitigation and effective treatments for CIPN can be aided by suitable in vitro assays. To this end, we developed a multiparametric morphology-centered rat dorsal root ganglion (DRG) assay. Morphologic alterations in subcellular structures of neurons and non-neurons were analyzed with an automated microscopy system. Stains for NeuN (a neuron-specific nuclear protein) and Tuj-1 (β-III tubulin) were used to identify neuronal cell nuclei and neuronal cell bodies/neurites, respectively...
January 22, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28104535/immune-mediated-processes-implicated-in-chemotherapy-induced-peripheral-neuropathy
#16
REVIEW
Justin G Lees, Preet G S Makker, Ryan S Tonkin, Munawwar Abdulla, Susanna B Park, David Goldstein, Gila Moalem-Taylor
Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain are challenging complications of cancer treatment. Many of the major classes of chemotherapeutics can cause neurotoxicity and significantly modulate the immune system. There is ongoing investigation regarding whether reciprocal crosstalk between the nervous and immune systems occurs and, indeed, contributes to neuropathic pain during treatment with chemotherapeutics. An emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28103821/genetic-polymorphisms-of-scn9a-are-associated-with-oxaliplatin-induced-neuropathy
#17
María Sereno, Gerardo Gutiérrez-Gutiérrez, Juan Moreno Rubio, María Apellániz-Ruiz, Lara Sánchez-Barroso, Enrique Casado, Sandra Falagan, Miriam López-Gómez, María Merino, César Gómez-Raposo, Nuria Rodriguez-Salas, Francisco Zambrana Tébar, Cristina Rodríguez-Antona
BACKGROUND: Oxaliplatin is a chemotherapy agent active against digestive tumors. Peripheral neuropathy is one of the most important dose-limiting toxicity of this drug. It occurs in around 60-80% of the patients, and 15% of them develop severe neuropathy. The pathophysiology of oxaliplatin neurotoxicity remains unclear. SCN9A is a gene codifying for a subtype sodium channel (type IX, subunit α) and mutations in this gene are involved in neuropathic perception. In this study we investigated whether SCN9A genetic variants were associated with risk of neurotoxicity in patients diagnosed of cancer on treatment with oxaliplatin...
January 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28094765/selective-antagonism-of-muscarinic-receptors-is-neuroprotective-in-peripheral-neuropathy
#18
Nigel A Calcutt, Darrell R Smith, Katie Frizzi, Mohammad Golam Sabbir, Subir K Roy Chowdhury, Teresa Mixcoatl-Zecuatl, Ali Saleh, Nabeel Muttalib, Randy Van der Ploeg, Joseline Ochoa, Allison Gopaul, Lori Tessler, Jürgen Wess, Corinne G Jolivalt, Paul Fernyhough
Sensory neurons have the capacity to produce, release, and respond to acetylcholine (ACh), but the functional role of cholinergic systems in adult mammalian peripheral sensory nerves has not been established. Here, we have reported that neurite outgrowth from adult sensory neurons that were maintained under subsaturating neurotrophic factor conditions operates under cholinergic constraint that is mediated by muscarinic receptor-dependent regulation of mitochondrial function via AMPK. Sensory neurons from mice lacking the muscarinic ACh type 1 receptor (M1R) exhibited enhanced neurite outgrowth, confirming the role of M1R in tonic suppression of axonal plasticity...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28088201/anti-allodynic-effect-of-buja-in-a-rat-model-of-oxaliplatin-induced-peripheral-neuropathy-via-spinal-astrocytes-and-pro-inflammatory-cytokines-suppression
#19
Yongjae Jung, Ji Hwan Lee, Woojin Kim, Sang Hyub Yoon, Sun Kwang Kim
BACKGROUND: Oxaliplatin, a widely used anticancer drug against metastatic colorectal cancer, can induce acute peripheral neuropathy, which is characterized by cold and mechanical allodynia. Activation of glial cells (e.g. astrocytes and microglia) and increase of pro-inflammatory cytokines (e.g. IL-1β and TNF-α) in the spinal cord play a crucial role in the pathogenesis of neuropathic pain. Our previous study demonstrated that Gyejigachulbu-Tang (GBT), a herbal complex formula, alleviates oxaliplatin-induced neuropathic pain in rats by suppressing spinal glial activation...
January 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28053885/shakuyakukanzoto-attenuates-oxaliplatin-induced-cold-dysesthesia-by-inhibiting-the-expression-of-transient-receptor-potential-melastatin-8-in-mice
#20
Tsugunobu Andoh, Shizuka Mizoguchi, Yasushi Kuraishi
Oxaliplatin-induced peripheral neuropathy characterized especially as cold dysesthesia is a major dose-limiting side effect of the drug and is very difficult to control. In the present study, we examined whether the traditional herbal formulation Shakuyakukanzoto (SKT: Sháo Yào Gān Cǎo Tāng) could relieve oxaliplatin-induced cold dysesthesia in mice. The inhibitory mechanisms were also investigated. Repetitive administration of SKT (0.1-1.0 g/kg) starting from the day after oxaliplatin injection inhibited cold dysesthesia in a dose-dependent manner...
January 2017: Journal of Traditional and Complementary Medicine
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