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Drug induced peripheral neuropathy

Zachary Curry, Jenny Wilkerson, Deniz Bagdas, Sarah Kyte, Nipa Patel, Giulia Donvito, Mohammed A Mustafa, Justin Poklis, Micah Niphakis, Ku-Lung Hsu, Benjamin F Cravatt, David A Gewirtz, M Imad Damaj, Aron H Lichtman
Although paclitaxel effectively treats various cancers, its debilitating peripheral neuropathic pain side effects often persist long after treatment has ended. Therefore, a compelling need exists for the identification of novel pharmacologic strategies to mitigate this condition. As inhibitors of monoacylglycerol lipase (MAGL), the primary hydrolytic enzyme of the endogenous cannabinoid 2-arachidonyolglycerol, produce antinociceptive effects in numerous rodent models of pain, we investigated whether inhibitors of this enzyme (i...
March 14, 2018: Journal of Pharmacology and Experimental Therapeutics
Lin Zhou, Yahui Hu, Chengyuan Li, Yunyi Yan, Luyao Ao, Boyang Yu, Weirong Fang, Jihua Liu, Yunman Li
Vincristine is a commonly used chemotherapeutic drug that can produce painful peripheral neuropathy. The chemokine (C-X-C motif) ligand 1 (CXCL1) and its receptor chemokine (C-X-C motif) receptor 2 (CXCR2) may mediate the resolution of this inflammation. In this study, we investigated whether and how CXCL1 contributes to vincristine-induced pain and the underlying mechanisms of levo-corydalmine (l-CDL, a tetrahydroprotoberberine). Oxycodone hydrochloride (a semisynthetic opioid analgesic) was used as positive control in vivo experiments...
March 5, 2018: Neuropharmacology
Roxanne J Wadia, Marilyn Stolar, Clarice Grens, Barbara E Ehrlich, Herta H Chao
Peripheral neuropathy is a major adverse effect in the use of chemotherapeutic drugs. In nearly 50% of patients, chemotherapy induced peripheral neuropathy (CIPN) has been reported as irreversible. With increasing numbers of patients surviving treatment as well as increasing duration of survival after treatment, reducing the side effects of chemotherapy and improving the quality of life has become a major focus of cancer survivorship. Multiple classes of chemotherapeutic drugs including taxanes, platinum agents and vinka alkaloids list peripheral neuropathy as the main dose-limiting side effect of treatment...
January 26, 2018: Oncotarget
Ellen M Lavoie Smith, Robert Knoerl, James J Yang, Grace Kanzawa-Lee, Deborah Lee, Celia M Bridges
PURPOSE: To test a reduced version-CIPN15-of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy scale (QLQ-CIPN20) to establish a possible gold-standard patient-reported outcome measure for chemotherapy-induced peripheral neuropathy (CIPN). METHODS: Using a prospective, longitudinal, case-control design, patients (n = 121) receiving neurotoxic chemotherapy completed the CIPN15 at baseline and 12 weeks and underwent objective neurological assessment using the 5-item Total Neuropathy Score-Clinical (TNSc)...
January 2018: Cancer Control: Journal of the Moffitt Cancer Center
Claudia Sommer, Christian Geber, Peter Young, Raimund Forst, Frank Birklein, Benedikt Schoser
BACKGROUND: Polyneuropathies (peripheral neuropathies) are the most common type of disorder of the peripheral nervous system in adults, and specifically in the elderly, with an estimated prevalence of 5-8%, depending on age. The options for treatment depend on the cause, which should therefore be identified as precisely as possible by an appropriate diagnostic evaluation. METHODS: This review is based on the current guidelines and on large-scale cohort studies and randomized, controlled trials published from 2000 to 2017, with an emphasis on non-hereditary types of polyneuropathy, that were retrieved by a selective search in PubMed...
February 9, 2018: Deutsches Ärzteblatt International
Anil Kumar, Harshpreet Kaur, Arti Singh
Neuropathic Pain (NP) is a painful condition which is a direct consequence of a lesion or disease affecting the somatosensory system with symptoms like allodynia, hyperalgesia. It has complex pathogenesis as it involves several molecular signaling pathways, thus numerous reliable animal models are crucial to understand the underlying mechanism of NP and formulate effective management therapy. Some models like spinal cord injury, chronic constriction injury, spinal nerve ligation, chemotherapy induced peripheral neuropathy, diabetes-induced NP and many more are discussed...
October 2, 2017: Pharmacological Reports: PR
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
Yasunori Minami, Masatoshi Kudo
Cryoglobulins are produced by the over-stimulated immune system of patients with hepatitis C virus (HCV). HCV-induced cryoglobulinemic vasculitis primarily affects small-sized vessels of systemic organs. The most common symptoms are purpura, joint pain, and peripheral neuropathy or Raynaud phenomenon. The blood tests of patients with HCV may exhibit raised erythrocyte sedimentation rate and C-reactive protein levels, positive rheumatoid factor and cryoglobulins, and decreased complement levels. Therapeutic options for HCV-induced cryoglobulinemic vasculitis, include anti-virals, Rituximab, steroids, immunosuppressant drugs, and plasma exchange...
February 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
Chelsea Snyder, Lanlan Yu, Tin Ngo, Daniel Sheinson, Yuda Zhu, Min Tseng, Dinah Misner, Karin Staflin
Neurotoxicity is a major concern during drug development, and together with liver and cardio-toxicity, it is one of the main causes of clinical drug attrition. Current pre-clinical models may not sufficiently identify and predict the risk for central or peripheral nervous system toxicity. One such example is clinically dose-limiting neuropathic effects after the administration of chemotherapeutic agents. Thus, the need to establish novel in vitro tools to evaluate the risk of neurotoxicities, such as neuropathy, remains unmet in drug discovery...
February 7, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Ami Tabata, Masashi Kanai, Takahiro Horimatsu, Tadao Tsuboyama, Kanae Matsushima, Toshihiro Kato
PURPOSE: Oxaliplatin, an important chemotherapeutic agent in colorectal cancer, causes chemotherapy-induced peripheral neuropathy (CIPN), for which prophylactic or therapeutic interventions are lacking. We aimed to investigate changes in upper extremities, activities of daily living (ADL), and health-related quality of life (HRQoL) parameters after the first chemotherapy cycle. METHODS: Thirty-eight colorectal cancer patients scheduled to receive the leucovorin, 5'-fluorouracil, oxaliplatin (FOLFOX) therapy or the capecitabine, oxaliplatin (CAPOX) therapy, participated...
February 8, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Nobushige Yabe, Eri Tamura, Keiichiro Kitahama, Hiroki Ozawa, Yuki Tajima, Takashi Takenoya, Ippei Oto, Takahisa Yoshikawa, Kenji Kojima, Shinji Murai, Hirotoshi Hasegawa, Yuko Kitagawa
A man aged 66 years presented with pneumaturia as a major complaint. Cancer of the sigmoid colon with infiltration to the urinary bladder was diagnosed and the patient underwent colectomy of the sigmoid colon and partial cystectomy of the bladder in May 2015. Histopathologic examinations revealed pT4b, Si(bladder), pN(-), cM0, fStage II . Because intestinal sub-obstruction and lymphatic invasion were present, CapeOX was administered as an adjunctive chemotherapy for the high-risk Stage II cancer. Because Grade 2 peripheral neuropathy appeared as a side effect, the dose was decreased to 80% from the 3 cycle...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Basak Donertas, Cigdem Cengelli Unel, Sule Aydin, Emel Ulupinar, Orhan Ozatik, Bilgin Kaygisiz, Engin Yildirim, Kevser Erol
Cisplatin is a widely-used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well-known side effect of cisplatin and has potential to result in limiting and/or reducing the dose, decreasing the quality of life. Thus, effective treatments are needed. Agmatine is an endogenous neuromodulator has been shown to exert antiallodynic effects in various animal studies. The first aim of this study was to investigate the in vitro effects of agmatine on cisplatin-induced neurotoxicity...
January 29, 2018: Fundamental & Clinical Pharmacology
F Resta, L Micheli, A Laurino, V Spinelli, T Mello, L Sartiani, L Di Cesare Mannelli, E Cerbai, C Ghelardini, M N Romanelli, G Mannaioni, A Masi
Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Understandably, developing new drugs targeting CIPN-specific pathogenic mechanisms would dramatically improve efficacy and tolerability of anti-neuropathic therapies...
January 12, 2018: Neuropharmacology
Sreenivasulu Palugulla, Steven Aibor Dkhar, Smita Kayal, Sunil K Narayan
Purpose: The aim of the current study is to report our prospective experience on the prevalence of oxaliplatin-induced peripheral neuropathy (OXAIPN) in patients with digestive tract cancers treated with oxaliplatin-based combination therapy. Materials and Methods: A total of 219 patients scheduled to be treated with oxaliplatin-based combination therapy were prospectively examined at baseline and follow-up during the therapy between November 2014 and December 2016...
October 2017: Indian Journal of Medical and Paediatric Oncology
Sherifa Ahmed Hamed
Drug-induced peripheral neuropathy had been rarely reported as an adverse effect of some antiepileptic drugs (AEDs) at high cumulative doses or even within the therapeutic drug doses or levels. We describe clinical and diagnostic features of a patient with peripheral neuropathy as an adverse effect of chronic topiramate (TPM) therapy. A 37-year-old woman was presented for the control of active epilepsy (2010). She was resistant to some AEDs as mono- or combined therapies (carbamazepine, sodium valproate, levetiracetam, oxcarbazepine and lamotrigine)...
December 16, 2017: World Journal of Clinical Cases
S Al-Mazidi, M Alotaibi, T Nedjadi, A Chaudhary, M Alzoghaibi, L Djouhri
BACKGROUND: Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a serious dose-limiting neurotoxic effect of cancer drug treatment. The underlying mechanism(s) of this debilitating condition, which lacks effective drug treatment, is incompletely understood. However, neural-immune interactions, involving increased expression and release of cytokines, are believed to be involved. Here, we examined, in the paclitaxel rat model of CIPNP, whether plasma levels of 24 cytokines/chemokines change after paclitaxel treatment, and whether blocking of signalling of some of those cytokines would reverse/attenuate behavioural signs of CIPNP...
December 27, 2017: European Journal of Pain: EJP
Anna Rapacz, Jolanta Obniska, Paulina Koczurkiewicz, Katarzyna Wójcik-Pszczoła, Agata Siwek, Anna Gryboś, Sabina Rybka, Aleksandra Karcz, Elżbieta Pękala, Barbara Filipek
Anticonvulsant drugs are used to treat a wide range of non-epileptic conditions, including chronic pain. The aim of the present experiments was to examine analgesic activity of three new 3,3-diphenyl-propionamides, which had previously demonstrated anticonvulsant activity in the MES (maximal electroshock seizure), scPTZ (subcutaneous pentylenetetrazole) and/or 6Hz (psychomotor seizure) tests in mice. Antinociceptive activity was examined in mouse models of acute pain (the hot plate test) and tonic pain (the formalin test) in mice...
December 17, 2017: European Journal of Pharmacology
Rafaela Scalco Ferreira, Neife Aparecida Guinaim Dos Santos, Nádia Maria Martins, Laís Silva Fernandes, Antonio Cardozo Dos Santos
Cisplatin is a highly effective chemotherapeutic drug that is toxic to the peripheral nervous system. Findings suggest that axons are early targets of the neurotoxicity of cisplatin. Although many compounds have been reported as neuroprotective, there is no effective treatment against the neurotoxicity of cisplatin. Caffeic acid phenethyl ester (CAPE) is a propolis component with neuroprotective potential mainly attributed to antioxidant and anti-inflammatory mechanisms. We have recently demonstrated the neurotrophic potential of CAPE in a cellular model of neurotoxicity related to Parkinson's disease...
December 19, 2017: Neurotoxicity Research
M J Ibañez-Juliá, G Berzero, G Reyes-Botero, T Maisonobe, T Lenglet, M Slim, S Louis, A Balaguer, M Sanson, E Le Guern, P Latour, D Ricard, T Stojkovic, D Psimaras
BACKGROUND: Charcot Marie Tooth (CMT) disease is the most common form of hereditary neuropathy. Due to the high prevalence of mild and undiagnosed forms, patients with CMT disease may be exposed to severe neurotoxicity following the administration of neurotoxic chemotherapies. The aim of this report is to alert oncologists to the potential to precipitate severe irreversible peripheral neuropathies when administering neurotoxic compounds to undiagnosed CMT patients. MATERIAL AND METHODS: A retrospective research in the OncoNeuroTox database was performed (2010-2016), searching for patients with the diagnosis of chemotherapy-induced peripheral neuropathy (CIPN) and CMT disease...
March 2018: Acta Oncologica
Ian R Kleckner, Charles Kamen, Jennifer S Gewandter, Nimish A Mohile, Charles E Heckler, Eva Culakova, Chunkit Fung, Michelle C Janelsins, Matthew Asare, Po-Ju Lin, Pavan S Reddy, Jeffrey Giguere, Jeffrey Berenberg, Shelli R Kesler, Karen M Mustian
PURPOSE: Over half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms...
December 14, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
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