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Pain nerve blockers

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https://www.readbyqxmd.com/read/28526335/the-spider-toxin-ph%C3%AE-1%C3%AE-recombinant-possesses-strong-analgesic-activity
#1
Flavia Karine Rigo, Gabriela Trevisan, Samira Dal-Toé De Prá, Marta Nascimento Cordeiro, Marcia Helena Borges, Juliana Figueiredo Silva, Flavia Viana Santa Cecilia, Alessandra Hubner de Souza, Gabriela de Oliveira Adamante, Alessandra Marcon Milioli, Célio José de Castro Junior, Juliano Ferreira, Marcus Vinicius Gomez
The native Phα1β - a Voltage-Gated Calcium Channel (VGCC) blocker - and its Recombinant Version - were both tested in rodent pain models with an intraplantar injections of capsaicin or formalin, a chronic constriction injury, and melanoma cancer related pain. The formalin nociceptive behaviour in the neurogenic phase was not affected by the toxin pre-treatments, while in the inflammatory phase, Phα1β and the Recombinant form caused a significant reduction. The nociception that was triggered by capsaicin, an agonist of the TRPV1 vanilloid receptor, was totally blocked by 100 pmol/site, i...
May 16, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28526152/pharmacologic-properties-of-novel-local-anesthetic-agents-in-anesthesia-practice
#2
REVIEW
Chih H King, Sascha S Beutler, Alan D Kaye, Richard D Urman
Therapeutic duration of traditional local anesthetics when used in peripheral nerve blocks is normally limited. This article describes novel approaches to extend the duration of peripheral nerve blocks currently available or in development. Three newer approaches on extending the duration of peripheral nerve blocks include site-1 sodium channel blockers, novel local anesthetics delivery systems, and novel adjuvants of local anesthetics. Compared with plain amide-based and ester-based local anesthetics, alternative approaches show significant promise in decreasing postoperative pain, rescue opioid requirement, hospital length-of-stay, and overall health care cost, without compromising the established safety profile of traditional local anesthetics...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28499411/paraneoplastic-acral-vascular-syndrome-in-a-patient-with-metastatic-melanoma-under-immune-checkpoint-blockade
#3
Thilo Gambichler, Stefanie Strutzmann, Andrea Tannapfel, Laura Susok
BACKGROUND: Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon which is observed in patients with adenocarcinomas and other malignancies. Various potential pathogenic mechanisms such as tumour invasion of sympathetic nerves, hyperviscosity, hypercoagulability, vasoactive tumour-secreted substances, and immunological mechanisms have been suggested. CASE PRESENTATION: We report a 60-year-old Caucasian male attended our hospital with a bulky lymph node mass in the right axilla...
May 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28496430/cholinergic-nociceptive-mechanisms-in-rat-meninges-and-trigeminal-ganglia-potential-implications-for-migraine-pain
#4
Irina Shelukhina, Nikita Mikhailov, Polina Abushik, Leniz Nurullin, Evgeny E Nikolsky, Rashid Giniatullin
BACKGROUND: Parasympathetic innervation of meninges and ability of carbachol, acetylcholine (ACh) receptor (AChR) agonist, to induce headaches suggests contribution of cholinergic mechanisms to primary headaches. However, neurochemical mechanisms of cholinergic regulation of peripheral nociception in meninges, origin place for headache, are almost unknown. METHODS: Using electrophysiology, calcium imaging, immunohistochemistry, and staining of meningeal mast cells, we studied effects of cholinergic agents on peripheral nociception in rat hemiskulls and isolated trigeminal neurons...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28450909/impact-of-gabapentin-on-neuronal-high-voltage-activated-ca-2-channel-properties-of-injured-side-axotomized-and-adjacent-uninjured-dorsal-root-ganglions-in-a-rat-model-of-spinal-nerve-ligation
#5
Minmin Zhu, Xiaodi Sun, Xiaodong Chen, Hang Xiao, Manlin Duan, Jianguo Xu
The density and properties of ion channels in the injured axon and dorsal root ganglion (DRG) neuronal soma membrane change following nerve injury, which may result in the development of neuropathic pain. Gabapentin (GBP) is a drug for the first-line treatment of neuropathic pain. One of its therapeutic targets is the voltage-activated calcium channel (VACC). In the present study, the whole-cell patch clamp technique was used to examine the changes of high voltage-activated Ca(2+) (HVA-Ca(2+)) channels in DRG neurons from sham and neuropathic rats in the absence and presence of GBP...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28214378/calcium-signaling-through-l-type-calcium-channels-role-in-pathophysiology-of-spinal-nociceptive-transmission
#6
REVIEW
Olivier Roca-Lapirot, Houda Radwani, Franck Aby, Frédéric Nagy, Marc Landry Pascal Fossat
L-type voltage-gated calcium channels (VGCCs) are ubiquitous channels in the central nervous system. L-type calcium channels (LTCs) are mostly post-synaptic channels regulating neuronal firing and gene expression. They play a role in important physio-pathological processes such as learning and memory, Parkinson's disease, autism and, as recognized more recently, in the pathophysiology of pain processes. Classically, the fundamental role of these channels in cardiovascular functions has limited the use of classical molecules to treat LTC-dependent disorders...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28076964/trigeminal-neuralgia-diagnosis-and-treatment
#7
Stine Maarbjerg, Giulia Di Stefano, Lars Bendtsen, Giorgio Cruccu
Introduction Trigeminal neuralgia (TN) is characterized by touch-evoked unilateral brief shock-like paroxysmal pain in one or more divisions of the trigeminal nerve. In addition to the paroxysmal pain, some patients also have continuous pain. TN is divided into classical TN (CTN) and secondary TN (STN). Etiology and pathophysiology Demyelination of primary sensory trigeminal afferents in the root entry zone is the predominant pathophysiological mechanism. Most likely, demyelination paves the way for generation of ectopic impulses and ephaptic crosstalk...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28038937/cellular-permeation-of-large-molecules-mediated-by-trpm8-channels
#8
Daniel D McCoy, Radhika Palkar, Yuening Yang, Serra Ongun, David D McKemy
While most membrane channels are only capable of passing small ions, certain non-selective cation channels have been recently shown to have the capacity to permeate large cations. The mechanisms underlying large molecule permeation are unclear, but this property has been exploited pharmacologically to target molecules, such as nerve conduction blockers, to specific subsets of pain-sensing neurons (nociceptors) expressing the heat-gated transient receptor potential (TRP) channel TRPV1. However, it is not clear if the principal mediator of cold stimuli TRPM8 is capable of mediating the permeation large molecules across cell membranes, suggesting that TRPM8-positive nerves cannot be similarly targeted...
February 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28024908/hyp-17-a-novel-voltage-gated-sodium-channel-blocker-relieves-inflammatory-and-neuropathic-pain-in-rats
#9
Jee Youn Lee, Yoo Lim Kam, Jungae Oh, Dong Hyun Kim, Jin-Sung Choi, Hae Young Choi, Sungmin Han, Inchan Youn, Hea-Young Park Choo, Tae Young Yune
Clinical and experimental studies suggest that voltage-gated sodium channels (VGSCs) play a key role in the pathogenesis of neuropathic pain and that blocking agents against these channels can be potentially therapeutic. In the current study, we investigated whether a novel compound, (-)-2-Amino-1-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)-propan-1-one(HYP-17), binds to VGSCs and evaluated its inhibitory effect on Na(+) currents of the rat dorsal root ganglia (DRG) sensory neurons and its analgesic effect on inflammatory and neuropathic pain...
February 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28017670/presynaptic-facilitation-by-tetracaine-of-glutamatergic-spontaneous-excitatory-transmission-in-the-rat-spinal-substantia-gelatinosa-involvement-of-trpa1-channels
#10
Lian-Hua Piao, Tsugumi Fujita, Ting Yu, Eiichi Kumamoto
The amide-type local anesthetic (LA) lidocaine activates transient receptor potential (TRP) ankyrin-1 (TRPA1) channels to facilitate spontaneous L-glutamate release onto spinal substantia gelatinosa (SG) neurons, which play a crucial role in regulating nociceptive transmission. In contrast, the ester-type LA procaine reduces the spontaneous release of L-glutamate in SG neurons. In order to determine whether TRPA1 activation by LAs is specific to amide-types, we examined the actions of tetracaine, another ester-type LA, and other amide-type LAs on glutamatergic spontaneous excitatory transmission in SG neurons by focusing on TRP activation...
December 22, 2016: Brain Research
https://www.readbyqxmd.com/read/27984097/anti-allodynic-effect-of-mangiferin-in-neuropathic-rats-involvement-of-nitric-oxide-cyclic-gmp-atp-sensitive-k-channels-pathway-and-serotoninergic-system
#11
Antonio Espinosa de Los Monteros-Zuñiga, Teresa Izquierdo, Geovanna Nallely Quiñonez-Bastidas, Héctor Isaac Rocha-González, Beatriz Godínez-Chaparro
The neurobiology of neuropathic pain is caused by injury in the central or peripheral nervous system. Recent evidence points out that mangiferin shows anti-nociceptive effect in inflammatory pain. However, its role in inflammatory and neuropathic pain and the possible mechanisms of action are not yet established. The purpose of this study was to determine the possible anti-allodynic effect of mangiferin in rats with spinal nerve ligation (SNL). Furthermore, we sought to investigate the possible mechanisms of action that contribute to these effects...
October 28, 2016: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/27823932/n-and-l-type-calcium-channels-blocker-cilnidipine-ameliorates-neuropathic-pain
#12
Shohei Yamamoto, Yuma Suzuki, Hideki Ono, Kazuhiko Kume, Masahiro Ohsawa
Cilnidipine is a dihydropyridine derivative that inhibits N-type and L-type voltage-gated Ca(2+) channels (VDCCs). We recently reported that a selective N-type VDCC blocker attenuated the spinal long-term potentiation (LTP) of C-fiber-evoked field potentials recorded in the spinal dorsal horn of rats, which served as a model for examining synaptic function during central pain sensitization. In this study, we investigated the effects of cilnidipine on the changes related to neuropathic pain induced by nerve injury...
December 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27765616/chronic-intrathecal-infusion-of-t-type-calcium-channel-blockers-attenuates-cav3-2-upregulation-in-nerve-ligated-rats
#13
Sheng-Jie Shiue, Chi-Hsu Wang, Tao-Yeuan Wang, Yi-Chun Chen, Jen-Kun Cheng
OBJECTIVE: T-type channel (TCC) CaV3.2 plays a pivotal role in pain transmission. In this study, we examined the effects of intrathecal TCC blockers on CaV3.2 expression in a L5/6 spinal nerve ligation (SNL) pain model. The neurotoxicity of TCC blockers were also evaluated. METHODS: Male Sprague-Dawley rats (200-250 g) were used for right L5/6 SNL to induce neuropathic pain. Intrathecal infusion of saline or TCC blockers [mibefradil (0.7 μg/h) or ethosuximide (60 μg/h)] was started after surgery for 7 days...
September 2016: Acta Anaesthesiologica Taiwanica: Official Journal of the Taiwan Society of Anesthesiologists
https://www.readbyqxmd.com/read/27730452/emerging-targets-for-the-management-of-osteoarthritis-pain
#14
REVIEW
Anne-Marie Malfait, Richard J Miller
Worldwide, osteoarthritis (OA) is one of the leading causes of chronic pain, for which adequate relief is not available. Ongoing peripheral input from the affected joint is a major factor in OA-associated pain. Therefore, this review focuses predominantly on peripheral targets emerging in the preclinical and clinical arena. Nerve growth factor is the most advanced of these targets, and its blockade has shown tremendous promise in clinical trials in knee OA. A number of different types of ion channels, including voltage-gated sodium channels and calcium channels, transient receptor potential channels, and acid-sensing ion channels, are important for neuronal excitability and play a role in pain genesis...
December 2016: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/27629721/spinal-fbxo3-dependent-fbxl2-ubiquitination-of-active-zone-protein-rim1%C3%AE-mediates-neuropathic-allodynia-through-cav2-2-activation
#15
Cheng-Yuan Lai, Yu-Cheng Ho, Ming-Chun Hsieh, Hsueh-Hsiao Wang, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
UNLABELLED: Spinal plasticity, a key process mediating neuropathic pain development, requires ubiquitination-dependent protein turnover. Presynaptic active zone proteins have a crucial role in regulating vesicle exocytosis, which is essential for synaptic plasticity. Nevertheless, the mechanism for ubiquitination-regulated turnover of presynaptic active zone proteins in the progression of spinal plasticity-associated neuropathic pain remains unclear. Here, after research involving Sprague Dawley rats, we reported that spinal nerve ligation (SNL), in addition to causing allodynia, enhances the Rab3-interactive molecule-1α (RIM1α), a major active zone protein presumed to regulate neural plasticity, specifically in the synaptic plasma membranes (SPMs) of the ipsilateral dorsal horn...
September 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27576790/challenges-to-develop-novel-anti-inflammatory-and-analgesic-drugs
#16
REVIEW
Bálint Botz, Kata Bölcskei, Zsuzsanna Helyes
Chronic inflammatory diseases and persistent pain of different origin represent common medical, social, and economic burden, and their pharmacotherapy is still an unresolved issue. Therefore, there is a great and urgent need to develop anti-inflammatory and analgesic agents with novel mechanisms of action, but it is a very challenging task. The main problem is the relatively large translational gap between the preclinical experimental data and the clinical results due to characteristics of the models, difficulties with the investigational techniques particularly for pain, as well as species differences in the mechanisms...
August 31, 2016: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/27542339/inhibition-of-hcn-channel-activity-in-the-thalamus-attenuates-chronic-pain-in-rats
#17
Weihua Ding, Zerong You, Shiqian Shen, Lucy Chen, Shengmei Zhu, Jianren Mao
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability in both peripheral and central nerve systems. Emerging evidence indicates that HCN channels are involved in the development and maintenance of chronic pain. However, the impact of HCN channel activity in the thalamus on chronic pain has not been examined. In this report, we evaluated the effect on nociceptive behaviors after infusion of a HCN channel blocker ZD7288 into the ventral posterolateral (VPL) nucleus of the thalamus in rats with neuropathic pain or monoarthritis...
September 19, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27434506/crotalphine-desensitizes-trpa1-ion-channels-to-alleviate-inflammatory-hyperalgesia
#18
Elisangela Bressan, Filip Touska, Irina Vetter, Katrin Kistner, Tatjana I Kichko, Nathália B Teixeira, Gisele Picolo, Yara Cury, Richard J Lewis, Michael J M Fischer, Katharina Zimmermann, Peter W Reeh
Crotalphine is a structural analogue to a novel analgesic peptide that was first identified in the crude venom from the South American rattlesnake Crotalus durissus terrificus. Although crotalphine's analgesic effect is well established, its direct mechanism of action remains unresolved. The aim of the present study was to investigate the effect of crotalphine on ion channels in peripheral pain pathways. We found that picomolar concentrations of crotalphine selectively activate heterologously expressed and native TRPA1 ion channels...
November 2016: Pain
https://www.readbyqxmd.com/read/27377721/p2x-receptors
#19
REVIEW
R Alan North
Extracellular adenosine 5'-triphosphate (ATP) activates cell surface P2X and P2Y receptors. P2X receptors are membrane ion channels preferably permeable to sodium, potassium and calcium that open within milliseconds of the binding of ATP. In molecular architecture, they form a unique structural family. The receptor is a trimer, the binding of ATP between subunits causes them to flex together within the ectodomain and separate in the membrane-spanning region so as to open a central channel. P2X receptors have a widespread tissue distribution...
August 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/27317871/gonyautoxins-first-evidence-in-pain-management-in-total-knee-arthroplasty
#20
Jaime Hinzpeter, Cristián Barrientos, Álvaro Zamorano, Álvaro Martinez, Miguel Palet, Rodrigo Wulf, Maximiliano Barahona, Joaquín M Sepúlveda, Matias Guerra, Tamara Bustamante, Miguel Del Campo, Eric Tapia, Nestor Lagos
Improvements in pain management techniques in the last decade have had a major impact on the practice of total knee arthroplasty (TKA). Gonyautoxin are phycotoxins, whose molecular mechanism of action is a reversible block of the voltage-gated sodium channels at the axonal level, impeding nerve impulse propagation. This study was designed to evaluate the clinical efficacy of Gonyautoxin infiltration, as a long acting pain blocker in TKA. Fifteen patients received a total dose of 40 μg of Gonyautoxin during the TKA operation...
September 1, 2016: Toxicon: Official Journal of the International Society on Toxinology
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