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https://www.readbyqxmd.com/read/29161016/selective-voltage-gated-sodium-channel-peptide-toxins-from-animal-venom-pharmacological-probes-and-analgesic-drug-development
#1
Ying Wu, Hui Ma, Fan Zhang, Chun-Lei Zhang, Xiaohan Zou, Zhengyu Cao
Voltage-gated sodium channels (Navs) play critical roles in action potential generation and propagation. Nav channelopathy as well as pathological sensitization contribute to allodynia and hyperalgesia. Recent evidence has demonstrated the significant roles of Nav subtypes (Nav1.3, 1.7, 1.8 and 1.9) in nociceptive transduction and therefore these Navs may represent attractive targets for analgesic drug discovery. Animal toxins are structurally diverse peptides that are highly potent yet selective on ion channel subtypes and therefore representing valuable probes to elucidate the structures, gating properties and cellular functions of ion channels...
November 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29160600/current-evidence-of-cannabinoid-based-analgesia-obtained-in-preclinical-and-human-experimental-settings
#2
REVIEW
J Lötsch, I Weyer-Menkhoff, I Tegeder
Cannabinoids have a long record of recreational and medical use and become increasingly approved for pain therapy. This development is based on preclinical and human experimental research summarized in this review. Cannabinoid CB1 receptors are widely expressed throughout the nociceptive system. Their activation by endogenous or exogenous cannabinoids modulates the release of neurotransmitters. This is reflected in antinociceptive effects of cannabinoids in preclinical models of inflammatory, cancer and neuropathic pain, and by nociceptive hypersensitivity of cannabinoid receptor-deficient mice...
November 21, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29160143/some-autonomic-deficits-of-acute-or-chronic-cervical-spinal-contusion-reversed-by-interim-brainstem-stimulation
#3
Alberto A Vitores, Stephanie S Sloley, Catalina Martinez, Melissa M Carballosa-Gautam, Ian D Hentall
Prolonged electrical stimulation of the hindbrain's nucleus raphe magnus (NRM) or its major midbrain input region, the periaqueductal gray (PAG), was previously found in rats to promote recovery from sensory-motor and histological deficits of acute thoracic spinal cord injury (SCI). Here, some visceral deficits of acute and chronic midline cervical (C5) contusion are similarly examined. Cranially implanted wireless stimulators delivered intermittent 8 Hz, 30-70 µA cathodal pulse trains to a brainstem microelectrode...
November 21, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29159784/g2a-as-a-threshold-regulator-of-inflammatory-hyperalgesia-modulates-chronic-hyperalgesia
#4
Yeu-Shiuan Su, Yu-Fen Huang, Jen Wong, Chia-Wei Lee, Wei-Shan Hsieh, Wei-Hsin Sun
Tissue injury, pathogen infection, and diseases are often accompanied by inflammation to release mediators that sensitize nociceptors and further recruit immune cells, which can lead to chronic hyperalgesia and inflammation. Tissue acidosis, occurring at the inflammatory site, is a major factor contributing to pain and hyperalgesia. The receptor G2 accumulation (G2A), expressed in neurons and immune cells, responds to protons or oxidized free fatty acids such as 9-hydroxyoctadecadienoic acid produced by injured cells or oxidative stresses...
November 21, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29159717/analgesic-anti-inflammatory-and-anticancer-activities-of-combretin-a-and-combretin-b-isolated-from-combretum-fragrans-f-hoffm-combretaceae-leaves
#5
Marius Mbiantcha, Jabeen Almas, Amadou Dawe, Aisha Faheem, Zafar Sidra
Previous pharmacological and phytochemical studies showed that, Combretum fragrans F. HOFFM (Combretaceae) is a Cameroonian medicinal plant possessing numerous therapeutic virtues and rich in various active secondary metabolites. In this study, we investigate in vivo anti-nociceptive and anti-inflammatory activity and, in vitro anticancer, anti-TNFα, ROS and NO-inhibitory activities of Combretum A and Combretin B, two triterpenes cycloartane-type isolated from the leaves of Combretum fragrans. The effect on ROS, TNF-α and NO production, anticancer activity and cytotoxicity assay were done using chemiluminescence technique, ELISA kit, colorimetric method, MCF-7 cells and MTT assay, respectively...
November 20, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/29158567/optogenetic-silencing-of-nociceptive-primary-afferents-reduces-evoked-and-ongoing-bladder-pain
#6
Vijay K Samineni, Aaron D Mickle, Jangyeol Yoon, Jose G Grajales-Reyes, Melanie Y Pullen, Kaitlyn E Crawford, Kyung Nim Noh, Graydon B Gereau, Sherri K Vogt, H Henry Lai, John A Rogers, Robert W Gereau
Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) suffer from chronic pain that severely affects quality of life. Although the underlying pathophysiology is not well understood, inhibition of bladder sensory afferents temporarily relieves pain. Here, we explored the possibility that optogenetic inhibition of nociceptive sensory afferents could be used to modulate bladder pain. The light-activated inhibitory proton pump Archaerhodopsin (Arch) was expressed under control of the sensory neuron-specific sodium channel (sns) gene to selectively silence these neurons...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29156922/changes-in-laser-evoked-potentials-during-hypnotic-analgesia-for-chronic-pain-a-pilot-study
#7
Giovanna Squintani, Maria P Brugnoli, Emanuela Pasin, Alessia Segatti, Elisa Concon, Enrico Polati, Bruno Bonetti, Angela Matinella
BACKGROUND: Hypnotic analgesia is one of the most effective nonpharmacological methods for pain control. Hypnosis and distraction of attention from pain might share similar mechanisms by which brain responses to painful stimulation could be similarly reduced in both states. There is ample evidence for the efficacy of clinical hypnosis as a psychological intervention in the treatment of acute or chronic pain. Results are conflicting, however, with some studies showing an increase, others a reduction, and others still no change in the amplitude of event-related brain potentials during hypnosis as compared to control conditions...
November 10, 2017: Annals of Palliative Medicine
https://www.readbyqxmd.com/read/29155276/cortical-plasticity-as-a-basis-of-phantom-limb-pain-fact-or-fiction
#8
J Andoh, C Milde, J W Tsao, H Flor
Cortical reorganization has been proposed as a major factor involved in phantom pain with prior nociceptive input to the deafferented region and input from the non-deafferented cortex creating neuronal activity that is perceived as phantom pain. There is substantial evidence that these processes play a role in neuropathic pain, although causal evidence is lacking. Recently it has been suggested that a maintenance of the cortical representation of the former hand area is related to phantom pain. Although interesting, evidence for this process is so far scarce...
November 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/29154689/peripheral-vagal-nerve-stimulation-modulates-the-nociceptive-withdrawal-reflex-in-healthy-subjects-a-randomized-cross-over-sham-controlled-study
#9
Roberto De Icco, Daniele Martinelli, Vito Bitetto, Mauro Fresia, Eric Liebler, Giorgio Sandrini, Cristina Tassorelli
Introduction The mechanism of action of non-invasive vagal nerve stimulation in the treatment of migraine is elusive. We studied its effect in a human model of pain, the nociceptive withdrawal reflex. Methods We enrolled 10 healthy subjects who underwent active non-invasive vagal nerve stimulation and sham treatment in a randomized, cross-over, sham-controlled study. Non-invasive vagal nerve stimulation was delivered with gammaCore®. The assessment of the nociceptive withdrawal reflex was performed at baseline (T0) and at 5 (T5) and 30 (T30) minutes after stimulation...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29153925/lateral-atlantoaxial-joint-meniscoid-volume-in-individuals-with-whiplash-associated-disorder-a-case-control-study
#10
Scott F Farrell, Subaat Khan, Peter G Osmotherly, Michele Sterling, Jon Cornwall, Darren A Rivett
BACKGROUND: Lateral atlantoaxial (LAA) joints are established sources of nociceptive input in chronic whiplash associated disorder (WAD). These joints contain intra-articular meniscoids that may be damaged in whiplash trauma. LAA joint meniscoid morphology has not been investigated comprehensively in a chronic WAD population, and it is unclear whether morphological differences exist compared to a pain-free population. OBJECTIVES: This study examined LAA joint meniscoid volume in individuals with chronic WAD who report pain in a distribution consistent with LAA joint pain...
November 10, 2017: Musculoskeletal Science & Practice
https://www.readbyqxmd.com/read/29151114/non-canonical-heterogeneous-cellular-distribution-and-co-localization-of-camkii%C3%AE-and-camkii%C3%AE-in-the-spinal-superficial-dorsal-horn
#11
Max Larsson
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a key enzyme in long-term plasticity in many neurons, including in the nociceptive circuitry of the spinal dorsal horn. However, although the role of CaMKII heterooligomers in neuronal plasticity is isoform-dependent, the distribution and co-localization of CaMKII isoforms in the dorsal horn have not been comprehensively investigated. Here, quantitative immunofluorescence analysis was used to examine the distribution of the two major neuronal CaMKII isoforms, α and β, in laminae I-III of the rat dorsal horn, with reference to inhibitory interneurons and neuronal populations defined by expression of parvalbumin, calretinin, and calbindin D28k...
November 18, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29150838/gi-530159-a-novel-selective-mechano-sensitive-k2p-channel-opener-reduces-rat-dorsal-root-ganglion-drg-neuron-excitability
#12
Alexandre J C Loucif, Pierre-Philippe Saintot, Jia Liu, Brett M Antonio, Shannon G Zellmer, Katrina Yoger, Emma L Veale, Anna Wilbrey, Kiyoyuki Omoto, Lishuang Cao, Alex Gutteridge, Neil A Castle, Edward B Stevens, Alistair Mathie
BACKGROUND AND PURPOSE: TREK two pore domain potassium channels play a critical role in regulating the excitability of somatosensory nociceptive neurons and are important mediators of pain perception. An understanding of the roles of TREK channels in pain perception and, indeed, in other pathophysiological conditions, has been severely hampered by the lack of potent and/or selective activators and inhibitors. In this study we describe a new, selective opener of TREK channels, GI-530159 (4,4'-(Hexafluoroisopropylidene)bis(p-phenyleneoxy)dianiline)...
November 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29149827/therapeutic-applications-of-capsaicin-in-upper-airways
#13
Carlo Cavaliere, Simonetta Masieri, Franco Cavaliere
Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the substance responsible of the irritation caused by the contact of chili peppers with the skin or mucous membranes. This protoalkaloid acts by stimulating the transient receptor potential cation channel subfamily V member 1 (TRPV1), which is mainly expressed by nociceptive fibers of peripheral sensory neurons, but is also present in the central nervous system, and in some non-neuronal cells. Following the initial, intense neuronal excitation, a brief refractory period occurs...
November 17, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/29149775/lentiviral-vectors-and-adeno-associated-virus-vectors-useful-tools-for-gene-transfer-in-pain-research
#14
REVIEW
Zheng Chen-Xi, Wang Sheng-Ming, Bai Yun-Hu, Luo Ting-Ting, Wang Jia-Qi, Dai Chun-Qiu, Guo Bao-Lin, Luo Shi-Cheng, Wang Dong-Hui, Yang Yan-Ling, Wang Ya-Yun
Pain, especially chronic pain, has always been a heated point in both basic and clinical researches since it puts heavy burdens on both individuals and the whole society. A better understanding of the role of biological molecules and various ionic channels involved in pain can shed light on the mechanism under pain and advocate the development of pain management. Using viral vectors to transfer specific genes at targeted sites is a promising method for both research and clinical applications. Lentiviral vectors and adeno-associated virus (AAV) vectors which allow stable and long-term expression of transgene in non-dividing cells are widely applied in pain research...
November 17, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/29149236/mutations-affecting-glycinergic-neurotransmission-in-hyperekplexia-increase-pain-sensitivity
#15
Pascal Henri Vuilleumier, Raphael Fritsche, Jürg Schliessbach, Bernhard Schmitt, Lars Arendt-Nielsen, Hanns Ulrich Zeilhofer, Michele Curatolo
Inhibitory interneurons in the spinal cord use glycine and GABA for fast inhibitory neurotransmission. While there is abundant research on these inhibitory pain pathways in animal models, their relevance in humans remains unclear, largely due to the limited possibility to manipulate selectively these pathways in humans. Hyperekplexia is a rare human disease that is caused by loss-of-function mutations in genes encoding for glycine receptors and glycine transporters. In the present study, we tested whether hyperekplexia patients display altered pain perception or central pain modulation compared with healthy subjects...
November 15, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29149144/the-efficacy-of-preoperative-gabapentin-in-spinal-surgery-a-meta-analysis-of-randomized-controlled-trials
#16
Chao Han, Ming-Jie Kuang, Jian-Xiong Ma, Xin-Long Ma
BACKGROUND: Pain management after spinal surgery has been studied for years. Gabapentin is a third-generation antiepileptic drug that selectively affects the nociceptive process and has been used for pain relief after surgery. However, the relationship between gabapentin and postoperative pain in spinal surgery is still controversial. OBJECTIVE: To assess the efficacy of the pre-emptive use of gabapentin in spinal surgery. STUDY DESIGN: A meta-analysis of randomized controlled studies...
November 2017: Pain Physician
https://www.readbyqxmd.com/read/29149031/anti-inflammatory-and-antinociceptive-effects-of-ethyl-acetate-fraction-of-an-edible-red-macroalgae-sarcodia-ceylanica
#17
Chieh-Chih Shih, Hwong-Ru Hwang, Chi-I Chang, Huei-Meei Su, Pei-Chin Chen, Hsiao-Mei Kuo, Pei-Jyuan Li, Hui-Min David Wang, Kuan-Hao Tsui, Yu-Chi Lin, Shi-Ying Huang, Zhi-Hong Wen
Research so far has only shown that edible red macroalgae, Sarcodia ceylanica has the ability to eliminate free radicals and anti-diabetic, anti-bacterial properties. This study was conducted both in vitro and in vivo on the ethyl acetate extract (PD1) of farmed red macroalgae in order to explore its anti-inflammatory properties. In order to study the in vitro anti-inflammatory effects of PD1, we used lipopolysaccharide (LPS) to induce inflammatory responses in murine macrophages. For evaluating the potential in vivo anti-inflammatory and antinociceptive effects of PD1, we used carrageenan-induced rat paw edema to produce inflammatory pain...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29147842/tetrandrine-alleviates-nociception-in-a-rat-model-of-migraine-via-suppressing-s100b-and-p-erk-activation-in-satellite-glial-cells-of-the-trigeminal-ganglia
#18
Guangcheng Qin, Bei Gui, Jingmei Xie, Lixue Chen, Lianlian Chen, Zhiwei Cui, Jiying Zhou, Ge Tan
Sensitization and activation of the trigeminal ganglia have been implicated in the pathology of migraine. Satellite glial cells (SGCs), a specialized type of glial cells that ensheathe trigeminal neurons, may be critical for peripheral nociceptive sensitization. Tetrandrine (TET), an alkaloid extracted from a traditional Chinese herb, exerts an inhibitory effect on glial activation in vitro and has been used in various neurologic diseases. The current study investigated the effect of TET on nitroglycerin (NTG)-induced trigeminal sensitization and examined potential signaling pathways related to SGC activation in the model of migraine...
November 16, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29146186/human-soluble-thrombomodulin-induced-blockade-of-peripheral-hmgb1-dependent-allodynia-in-mice-requires-both-the-lectin-like-and-egf-like-domains
#19
Yusuke Hayashi, Ryuichi Tsujita, Maho Tsubota, Haruka Saeki, Fumiko Sekiguchi, Goichi Honda, Atsufumi Kawabata
Thrombomodulin (TM), an endothelial protein with anti-coagulant activity, is composed of 5 domains, D1-D5. Recombinant human soluble TM (TMα) consisting of D1-D3, which is generated in CHO cells, suppresses inflammatory and nociceptive signals by inactivating high mobility group box 1 (HMGB1), one of damage-associated molecular patterns. TMα sequesters HMGB1 with the lectin-like D1 and promotes its degradation by thrombin binding to the EGF-like D2. We prepared TM's D123, D1 and D2 by the protein expression system of yeast, and evaluated their effects on HMGB1 degradation in vitro and on the allodynia caused by HMGB1 in distinct redox forms in mice in vivo...
November 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29145791/impact-of-novel-n-aryl-piperamide-no-donors-on-nf-%C3%AE%C2%BAb-translocation-in-neuroinflammation-rational-drug-designing-synthesis-and-biological-evaluation
#20
Sajad Shahbazi, Jagdeep Kaur, Shikha Singh, K Gopinath Achary, Sameena Wani, Sobhagyalaxmi Jema, Jabed Akhtar, Ranbir Chander Sobti
NO donor drugs showed a significant therapeutic effect in the treatment of many diseases, such as arteriopathies, various acute and chronic inflammatory conditions, and several degenerative diseases. NO-releasing anti-inflammatory drugs are the prototypes of a novel class of compounds, combining the pharmacological activities of anti-inflammatory and anti-nociceptive of drugs with those of NO, thus possessing potential therapeutic applications in a great variety of diseases. In this study, we designed and predicted biological activity by targeting cyclooxygenase type 2 (COX-2) and NF-κB subunits and pharmacological profiling along with toxicity predictions of various N-aryl piperamides linked via an ester bond to a spacer that is bound to a NO-releasing moiety (-ONO2)...
January 1, 2017: Innate Immunity
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