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Cancer induced neuropathic pain

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
Cristina Carrasco, Mustafa Naziroǧlu, Ana B Rodríguez, José A Pariente
Currently, neuropathic pain is an underestimated socioeconomic health problem affecting millions of people worldwide, which incidence may increase in the next years due to chronification of several diseases, such as cancer and diabetes. Growing evidence links neuropathic pain present in several disorders [i.e., spinal cord injury (SCI), cancer, diabetes and alcoholism] to central sensitization, as a global result of mitochondrial dysfunction induced by oxidative and nitrosative stress. Additionally, inflammatory signals and the overload in intracellular calcium ion could be also implicated in this complex network that has not yet been elucidated...
2018: Frontiers in Physiology
O Kambur, M A Kaunisto, B S Winsvold, T Wilsgaard, A Stubhaug, J A Zwart, E Kalso, C S Nielsen
P2X7 is a non-selective cation channel activated by extracellular ATP. P2X7 activation contributes to the pro-inflammatory response to injury or bacterial invasion and mediates apoptosis. Recently, P2X7 function has been linked to chronic inflammatory and neuropathic pain. P2X7 may contribute to pain modulation both by effects on peripheral tissue injury underlying clinical pain states, and through alterations in central nervous system processing, as suggested by animal models. To further test its role in pain sensitivity, we examined whether variation within the P2RX7 gene, which encodes the P2X7 receptor, was associated with experimentally induced pain in human patients...
February 20, 2018: Pain
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
Gaia Pasqualetto, Andrea Brancale, Mark T Young
P2X receptors are trimeric eukaryotic ATP-gated cation channels. Extracellular ATP-their physiological ligand-is released as a neurotransmitter and in conditions of cell damage such as inflammation, and substantial evidence implicates P2X receptors in diseases including neuropathic pain, cancer, and arthritis. In 2009, the first P2X crystal structure, Danio rerio P2X4 in the apo - state, was published, and this was followed in 2012 by the ATP-bound structure. These structures transformed our understanding of the conformational changes induced by ATP binding and the mechanism of ligand specificity, and enabled homology modeling of mammalian P2X receptors for ligand docking and rational design of receptor modulators...
2018: Frontiers in Pharmacology
J Fleisch, A Dahan
- Cancer patients often experience pain that has a significantly negative effect on their daily living.- This pain may be caused by the disease process itself, but may also be related to the treatment such as chemotherapy-induced neuropathic pain, chronic pain following surgery and post-amputation pain.- In this training article we will discuss the different aspects of cancer-related pain, based on various questions posed by general practitioners and internists.- Items that are discussed include measurement of pain, opioid therapy, opioid side effects, adjuvant medication, barriers that preclude proper treatment of pain, opioid tolerance and addiction, and interventional therapy...
2018: Nederlands Tijdschrift Voor Geneeskunde
Hideaki Yano, Alessandro Bonifazi, Min Xu, Daryl A Guthrie, Stephanie N Schneck, Ara M Abramyan, Andrew D Fant, W Conrad Hong, Amy H Newman, Lei Shi
The sigma 1 receptor (σ1R) is a structurally unique transmembrane protein that functions as a molecular chaperone in the endoplasmic reticulum (ER), and has been implicated in cancer, neuropathic pain, and psychostimulant abuse. Despite physiological and pharmacological significance, mechanistic underpinnings of structure-function relationships of σ1R are poorly understood, and molecular interactions of selective ligands with σ1R have not been elucidated. The recent crystallographic determination of σ1R as a homo-trimer provides the foundation for mechanistic elucidation at the molecular level...
January 30, 2018: Neuropharmacology
Luke P Legakis, John W Bigbee, S Stevens Negus
Paclitaxel is a cancer chemotherapy with adverse effects that include peripheral neuropathy, neuropathic pain, and depression of behavior and mood. In rodents, hypersensitive paw-withdrawal reflexes from mechanical stimuli serve as one common measure of paclitaxel-induced pain-related behavior. This study tested the hypothesis that paclitaxel would also depress rates of positively reinforced operant responding as a measure of pain-related behavioral depression. Male and female Sprague-Dawley rats were equipped with electrodes targeting the medial forebrain bundle, trained to lever press for electrical brain stimulation in an assay of intracranial self-stimulation (ICSS), and treated with four injections of varying paclitaxel doses (0...
January 23, 2018: Behavioural Pharmacology
Luke P Legakis, S Stevens Negus
Paclitaxel is a cancer chemotherapy drug with adverse effects that include chemotherapy-induced neuropathic pain (CINP) as well as depression of behavior and mood. In the clinical setting, opioids are often used concurrently with or following chemotherapy to treat pain related to the cancer or CINP, but repeated opioid exposure can also increase risk of opioid abuse. In this study, male and female Sprague Dawley rats were used to test the hypothesis that repeated 3.2 mg/kg morphine would induce tolerance to its antinociceptve effects in a mechanical sensitivity assay and increased expression of its abuse-related rewarding effects in an assay of intracranial self-stimulation (ICSS)...
January 23, 2018: Journal of Pharmacology and Experimental Therapeutics
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
Ling-Chun Lu, Sou-Yi Chang, Chieh-Yu Liu, Shiow-Luan Tsay
BACKGROUND/PURPOSE: Chemotherapy-induced peripheral neuropathy is a common consequence of chemotherapeutic treatments in patients with cancer. This study evaluated the validity and reliability of a Chinese version of the Neuropathic Pain Symptom Inventory (C-NPSI) in patients with colorectal cancer and chemotherapy-induced peripheral neuropathy. METHODS: This cross-sectional study recruited 106 patients from a cancer center in Northern Taiwan. The C-NPSI was obtained through the translation and back-translation of the original NPSI...
January 8, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Xue-Tao Yan, Jing-Min Lu, Yu Wang, Xiao-Li Cheng, Xiang-Hu He, Wen-Zhong Zheng, Hu Chen, Yan-Lin Wang
LncRNAs are reported to participate in neuropathic pain development. LncRNA X-inactive specific transcript (XIST) is involved in the progression of various cancers. However, the role of XIST in neuropathic pain remains unclear. In our present study, we established a chronic constriction injury (CCI) rat model and XIST was found to be greatly upregulated both in the spinal cord tissues and in the isolated microglias of CCI rats. Inhibition of XIST inhibited neuropathic pain behaviors including mechanical and thermal hyperalgesia...
January 11, 2018: Journal of Cellular Physiology
Alireza Abed, Mohammad Javad Khoshnoud, Mehdi Taghian, Mahbubeh Aliasgharzadeh, Azam Mesdaghinia
Objectives: Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient's survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects...
November 2017: Iranian Journal of Basic Medical Sciences
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
Lorenzo Di Cesare Mannelli, Barbara Tenci, Laura Micheli, Alessia Vona, Francesca Corti, Matteo Zanardelli, Andrea Lapucci, Ann Maria Clemente, Paola Failli, Carla Ghelardini
Oxaliplatin therapy of colorectal cancer induces a dose-dependent neuropathic syndrome in 50% of patients. Pharmacological treatments may offer limited relief; scientific efforts are needed for new therapeutic approaches. Therefore we evaluated in a preclinical setting the pain relieving properties of mesenchymal stem cells and its secretome. Rat adipose stem cells (rASCs) were administered in a rat model of oxaliplatin-induced neuropathy. A single intravenous injection of rASCs reduced oxaliplatin-dependent mechanical hypersensitivity to noxious and non-noxious stimuli taking effect 1 h after administration, peaking 6 h thereafter and lasting 5 days...
December 11, 2017: Neuropharmacology
Karli Montague, Marzia Malcangio
In cancer treatments a dose-limiting side-effect of chemotherapeutic agents is the development of neuropathic pain, which is poorly managed by clinically available drugs at present. Chemotherapy-induced painful neuropathy (CIPN) is a major cause of premature cessation of treatment and so a greater understanding of the underlying mechanisms and the development of novel, more effective therapies, is greatly needed. In some cases, only a weak correlation between chemotherapy-induced pain and neuronal damage is observed both clinically and preclinically...
2017: Frontiers in Molecular Neuroscience
Lisa H Trahan, Emily Cox-Martin, Carrie E Johnson, Patrick M Dougherty, Jun Yu, Lei Feng, Christina Cook, Diane M Novy
Purpose: The objectives of the study were to (1) assess the extent to which interrater reliability of pain drawing location and dispersion scoring methods are similar across pain disciplines in a sample of patients with cancer treatment-induced neuropathic pain ( N = 56) and (2) investigate indicators of validity of the pain drawing in this unique sample. Methods: Patients undergoing cancer therapy completed the Brief Pain Inventory Body Map, the MD Anderson Symptom Inventory, and the McGill Pain Questionnaire...
December 2017: Journal of Applied Biobehavioral Research
Paulina Nuñez-Badinez, Hugo Sepúlveda, Emilio Diaz, Wolfgang Greffrath, Rolf-Detlef Treede, Jimmy Stehberg, Martin Montecino, Brigitte van Zundert
The purinergic receptor P2X3 (P2X3-R) plays important roles in molecular pathways of pain, and reduction of its activity or expression effectively reduces chronic inflammatory and neuropathic pain sensation. Inflammation, nerve injury, and cancer-induced pain can increase P2X3-R mRNA and/or protein levels in dorsal root ganglia (DRG). However, P2X3-R expression is unaltered or even reduced in other pain studies. The reasons for these discrepancies are unknown and might depend on the applied traumatic intervention or on intrinsic factors such as age, gender, genetic background, and/or epigenetics...
December 8, 2017: Journal of Cellular Biochemistry
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
Vasiliki Brozou, Athina Vadalouca, Panagiotis Zis
INTRODUCTION: Platin-induced peripheral neuropathy (PIPN) is a common cause of PN in cancer patients. The aim of this paper is to systematically review the current literature regarding PIPN, with a particular focus on epidemiological and clinical characteristics of painful PIPN, and to discuss relevant management strategies. METHODS: A systematic computer-based literature search was conducted on the PubMed database. RESULTS: This search strategy resulted in the identification of 353 articles...
December 1, 2017: Pain and Therapy
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