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https://www.readbyqxmd.com/read/29346771/rapid-turnover-of-cortical-ncam1-regulates-synaptic-reorganization-after-peripheral-nerve-injury
#1
Hyoung-Gon Ko, Jun-Hyeok Choi, Dong Ik Park, SukJae Joshua Kang, Chae-Seok Lim, Su-Eon Sim, Jaehoon Shim, Ji-Il Kim, Siyong Kim, Tae-Hyeok Choi, Sanghyun Ye, Jaehyun Lee, Pojeong Park, Somi Kim, Jeehaeh Do, Jihye Park, Md Ariful Islam, Hyun Jeong Kim, Christoph W Turck, Graham L Collingridge, Min Zhuo, Bong-Kiun Kaang
Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized nociception. Although there is evidence that plastic changes in the cortex contribute to this process, the underlying molecular mechanisms are unclear. Here, we find that activation of the anterior cingulate cortex (ACC) induced by peripheral nerve injury increases the turnover of specific synaptic proteins in a persistent manner. We demonstrate that neural cell adhesion molecule 1 (NCAM1) is one of the molecules involved and show that it mediates spine reorganization and contributes to the behavioral sensitization...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29344649/effects-of-intrathecal-bupivacaine-on-the-nr2b-camkii%C3%AE-creb-signaling-pathway-in-the-rat-lumbar-spinal-cord
#2
Liyan Zhao, Yonghai Zhang, Fan Yang, Di Zhu, Ningkang Li, Li Zhao, Na Li, Jianqiang Yu, Hanxiang Ma
Neuraxial anesthesia produces an anesthetic-sparing, sedative effect. The mechanism underlying this effect potentially involves decreased spinal afferent input. However, the neurochemical mechanisms at the spinal level remain unknown. The N‑methyl‑D‑aspartate receptor 2B subunit/calcium‑calmodulin‑dependent protein kinase II α/cAMP response element‑binding protein (NR2B/CaMKIIα/CREB) signaling pathway serves an important role in regulating the transmittance of peripheral noxious stimulation to supraspinal regions in the process of nociception...
January 17, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29343985/bioactive-chromone-constituents-from-vitex-negundo-alleviate-pain-and-inflammation
#3
Ajmal Khan, Sadia Naz, Umar Farooq, Muhammad Shahid, Irfan Ullah, Iftikhar Ali, Abdur Rauf, Yahia Nasser Mabkhot
Background: Vitex negundo L. has been widely studied for its beneficial effect in inflammatory and pain conditions. The present study describes the isolation of two new bioactive chromone constituents from V. negundo and their in vivo evaluation for anti-inflammatory and antinociceptive activities. Methods: Two new chromone derivatives, namely, methyl 3-(2-(5-hydroxy-6-methoxy-4-oxo-4H-chromen-2-yl)ethyl)benzoate (1) and 3-(1-hydroxy-2-(5-hydroxy-6-methoxy-4-oxo-4H-chromen-2-yl)ethyl)benzoic acid (2) were isolated from V...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29343980/peripheral-and-spinal-trpa1-channels-contribute-to-formalin-induced-long-lasting-mechanical-hypersensitivity
#4
Vladimir A Martínez-Rojas, Guadalupe García, Roxana Noriega-Navarro, Crystell G Guzmán-Priego, Jorge E Torres-López, Vinicio Granados-Soto, Janet Murbartián
Background: Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed by a subset of nociceptive neurons that acts as a multimodal receptor. Its activity contributes to modulate nociceptive transmission in acute inflammatory pain. However, the role of this channel in chronic pain has been less studied. The purpose of this study was to investigate the local peripheral and spinal participation of TRPA1 channels in formalin-induced long-lasting hypersensitivity...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29343689/a-novel-%C3%AE-conopeptide-eu1-6-inhibits-n-type-cav2-2-calcium-channels-and-exhibits-potent-analgesic-activity
#5
Zhuguo Liu, Peter Bartels, Mahsa Sadeghi, Tianpeng Du, Qing Dai, Cui Zhu, Shuo Yu, Shuo Wang, Mingxin Dong, Ting Sun, Jiabin Guo, Shuangqing Peng, Ling Jiang, David J Adams, Qiuyun Dai
We here describe a novel α-conopeptide, Eu1.6 from Conus eburneus, which exhibits strong anti-nociceptive activity by an unexpected mechanism of action. Unlike other α-conopeptides that largely target nicotinic acetylcholine receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the α3β4 and α7 nAChR subtypes and TTX-resistant sodium channels, and no activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG) neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels expressed in HEK293 cells...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343477/role-of-asic3-nav1-7-and-nav1-8-in-electroacupuncture-induced-analgesia-in-a-mouse-model-of-fibromyalgia-pain
#6
Liang-Ta Yen, Yu-Chan Hsu, Jaung-Geng Lin, Ching-Liang Hsieh, Yi-Wen Lin
BACKGROUND: The mechanisms underlying fibromyalgia (FM) pain are not understood. The US Food and Drug Administration has recommended three drugs for treating FM-namely, pregabalin, duloxetine and milnacipran; however, these medications are associated with severe side effects. OBJECTIVE: To create a mouse model of FM pain using dual injections of acidic saline to cause mechanical hyperalgesia and test whether ASIC3, Nav1.7 and Nav1.8 are involved in this process and whether electroacupuncture (EA) can reverse these phenomena...
January 17, 2018: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
https://www.readbyqxmd.com/read/29343280/pregabalin-versus-placebo-in-targeting-pro-nociceptive-mechanisms-to-prevent-chronic-pain-after-whiplash-injury-in-at-risk-individuals-a-feasibility-study-for-a-randomised-controlled-trial
#7
J Nikles, G Keijzers, G Mitchell, S Schug, R Ware, S A McLean, L Connelly, S Gibson, S F Farrell, M Sterling
BACKGROUND: Whiplash-associated disorders (WAD) are an enormous and costly burden to Australian society. Up to 50% of people who experience a whiplash injury will never fully recover. Whiplash is resistant to treatment and no early management approach has yet been shown to prevent chronic pain. The early presence of central sensitization is associated with poor recovery. Pregabalin's effects on central sensitization indicate the potential to prevent or modulate these processes after whiplash injury and to improve health outcomes, but this has not been investigated...
January 17, 2018: Trials
https://www.readbyqxmd.com/read/29342105/neuroimmune-driven-neuropathic-pain-establishment-a-focus-on-gender-differences
#8
REVIEW
Vincenzo Coraggio, Francesca Guida, Serena Boccella, Mariantonietta Scafuro, Salvatore Paino, Domenico Romano, Sabatino Maione, Livio Luongo
The role of neuroinflammatory cells in the establishment of neuropathic pain has been investigated in depth in the last few years. In particular, microglia have been shown to be key players in the induction of tactile allodynia, as they release proinflammatory molecules that, in turn, sensitize nociceptive neurons within the spinal cord. However, the role of peripheral immune cells such as macrophages, infiltrating monocytes, mast cells, and T-cells has been highlighted in the last few studies, even though the data are still conflicting and need to be clarified...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29339457/curcumin-acts-as-a-positive-allosteric-modulator-of-%C3%AE-7-nicotinic-acetylcholine-receptors-and-reverses-nociception-in-mouse-models-of-inflammatory-pain
#9
Eslam Gaber El Nebrisi, Deniz Bagdas, Wisam Toma, Halima Al Samri, Anna Brodzik, Yasmin Alkhlaif, Keun-Hang Susan Yang, Frank C Howarth, Imad M Damaj, Murat Oz
Effects of curcumin, a major ingredient of turmeric, were tested on the function of α7 subunit of the human nicotinic acetylcholine (α7 nACh) receptor expressed in Xenopus oocytes and on nociception in mouse models of tonic and visceral pain. Curcumin caused a significant potentiation of ACh (100 μM)-induced currents with an EC50 value of 0.2 µM. The effect of curcumin was not dependent on the activation of G-proteins and protein kinases and did not involve Ca2+-dependent Cl- channels expressed endogenously in oocytes...
January 16, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29337220/botaf-a-new-buthus-occitanus-tunetanus-scorpion-toxin-produces-potent-analgesia-in-rodents
#10
Riadh Maatoug, Jed Jebali, Régis Guieu, Michel De Waard, Riadh Kharrat
This work reports the purification of new potent scorpion neuropeptide, named BotAF, by an activity-guided screening approach. BotAF is a 64-residue long-chain peptide that shares very high similarity with the original β-like scorpion toxin group, in which several peptides have been characterized to be anti-nociceptive in rodents. BotAF administration to rodents does not produce any toxicity or motor impairment, including at high doses. In all models investigated, BotAF turned out to be an efficient peptide in abolishing acute and inflammatory (both somatic and visceral) pain in rodents...
January 11, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29336505/signalling-transduction-events-involved-in-agonist-induced-pge2-ep4-receptor-externalization-in-cultured-rat-dorsal-root-ganglion-neurons
#11
W Ma, B St-Jacques
BACKGROUND: Prostaglandin E2 (PGE2) enriched in inflamed tissues contributes to chronic pain by sensitizing nociceptive dorsal root ganglion (DRG) neurons (nociceptors). Of four PGE2 receptors (EP1-4), EP4 plays a major role in PGE2-induced nociceptor sensitization. We have previously reported that PGE2 or EP4 agonists stimulated EP4 externalization in cultured DRG neurons and this event contributes to nociceptor sensitization. However, the signalling transduction events governing this event remain unknown...
January 16, 2018: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29335794/effect-of-a-calcitonin-gene-related-peptide-binding-l-rna-aptamer-on-neuronal-activity-in-the-rat-spinal-trigeminal-nucleus
#12
Michael J M Fischer, Jakob Schmidt, Stanislav Koulchitsky, Sven Klussmann, Axel Vater, Karl Messlinger
BACKGROUND: Calcitonin gene-related peptide (CGRP) plays a major role in the pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons integrate nociceptive afferent input from trigeminal tissues including intracranial afferents, and their activity is thought to reflect facial pain and headache in man. CGRP receptor inhibitors and anti-CGRP antibodies have been demonstrated to be therapeutically effective in migraine. In parallel, CGRP receptor inhibition has been shown to lower spinal trigeminal neuron activity in animal models of meningeal nociception...
January 15, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29335352/discrete-modules-and-mesoscale-functional-circuits-for-thermal-nociception-within-primate-s1-cortex
#13
Pai-Feng Yang, Ruiqi Wu, Tung-Lin Wu, Zhaoyue Shi, Li Min Chen
This study addresses one long-standing question of whether functional separations are preserved for somatosensory modalities of touch, heat and cold nociception within primate primary somatosensory (S1) cortex. This information is critical for understanding how the nature of pain is represented in the primate brain. Using a combination of submillimeter-resolution fMRI and microelectrode local field potential (LFP) and spike recordings, we identified spatially-segregated cortical zones for processing touch, nociceptive heat and cold stimuli in somatotopically appropriate areas 3a, 3b, 1, and 2 of S1 in male monkeys...
January 15, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29333821/opioid-treatment-for-mixed-pain-in-pediatric-patients-assisted-by-the-palliative-care-team-five-years-of-experience
#14
María L Yazde Puleio, Karina V Gómez, Ana Majdalani, Vilma Pigliapoco, Gisella Santos Chocler
Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Depending on its pathophysiological mechanism, it may be classified into nociceptive, neuropathic, and mixed pain. If pain is moderate to severe, a strong opioid should be administered and, when this is the case, morphine is the drug of choice. If morphine is ineffective or causes intolerable adverse effects, opioid rotation is recommended. Our objective was to describe the drug management for mixed pain used in patients assisted by the Palliative Care team of Hospital General de Niños Pedro de Elizalde between August 2011 and September 2015...
February 1, 2018: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/29333034/antinociceptive-and-anti-inflammatory-effects-of-triterpenes-from-pluchea-quitoc-dc-aerial-parts
#15
Francisco Alcione Nobre da Silva, Sônia Maria de Farias Freire, Marilene Oliveira da Rocha Borges, Francisco Erivaldo Vidal Barros, Maria da de Sousa, Maria Nilce de Sousa Ribeiro, Giselle Maria Skelding Pinheiro Guilhon, Adolfo Henrique Müller, Antonio Carlos Romão Borges
Background: Pluchea quitoc DC. (Asteraceae), a medicinal plant known as "quitoco," "caculucage," "tabacarana" and "madre-cravo," is indicated for inflammatory conditions such as bronchitis, arthritis, and inflammation in the uterus and digestive system. Objective: This study evaluated the analgesic and anti-inflammatory activities of the triterpenes compounds obtained from P. quitoc aerial parts. Materials and Methods: The triterpenes compounds β-amyrin, taraxasterol and pseudo-taraxasterol in a mixture (T); β-amyrin, taraxasterol and pseudo-taraxasterol acetates in a mixture (Ta); β-amyrin, taraxasterol, pseudo-taraxasterol acetates in a mixture with β-amyrin, taraxasterol and pseudo-taraxasterol myristates (Tafe) were analyzed in the models of nociception and inflammation...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29332567/nociceptin-orphanin-fq-peptide-nop-receptor-modulators-an-update-in-structure-activity-relationships
#16
Carlo Mustazza, Stefano Pieretti, Francesca Marzoli
Nociceptin /Orphanin FQ Peptide" receptor (NOPr) is a G-protein-coupled receptor with the nociceptin/orphanin FQ peptide (N/OFQ) as endogenous agonist. It is expressed in the nervous system as well as in some non-neural tissues. Its activation has pronociceptive effect at the supraspinal level, whereas at the spinal level it produces nociceptive effects at low doses and antinociceptive effects at higher doses. NOPr is also involved in mood and blood pressure regulation, immunoregulation, airway constriction, feeding, urination, bowel motility, learning and memory...
January 10, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29330156/application-of-receptor-theory-to-the-design-and-use-of-fixed-proportion-mu-opioid-agonist-and-antagonist-mixtures-in-rhesus-monkeys
#17
Jeremy C Cornelissen, Samuel Obeng, Kenner C Rice, Yan Zhang, S Stevens Negus, Matthew Banks
Receptor theory predicts that fixed-proportion mixtures of a competitive, reversible agonist (e.g. fentanyl) and antagonist (e.g. naltrexone) at a common receptor (e.g. mu opioid receptors; MOR) will result in antagonist proportion-dependent decreases in apparent efficacy of the mixtures and downward shifts in mixture dose-effect functions. The present study tested this hypothesis by evaluating behavioral effects of fixed-proportion fentanyl/naltrexone mixtures in a warm-water tail-withdrawal procedure in rhesus monkeys (n=4)...
January 12, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29329908/anatomical-evidence-for-lateral-hypothalamic-innervation-of-the-pontine-a7-catecholamine-cell-group-in-rat
#18
Janean E Holden, Monica A Wagner, Brady L Reeves
Substantial behavioral evidence exists to support the idea that the lateral hypothalamus (LH) makes axonal connection with spinally-projecting noradrenergic neurons of the A7 catecholamine cell group in the pons. Through this putative projection, the LH modulates nociception via α1- and α2-adrenoceptors in the dorsal horn. We used double-label immunocytochemistry to demonstrate that axons from the LH labeled with the anterograde tracer biotinylated dextran amine (BDA) appose tyrosine hydroxylase-immunoreactive (TH-ir) neuron profiles in the A7 area...
January 9, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29329072/development-of-potent-and-proteolytically-stable-human-neuromedin-u-receptor-agonists
#19
An De Prins, Charlotte Martin, Yannick Van Wanseele, Louise Julie Skov, Csaba Tömböly, Dirk Tourwé, Vicky Caveliers, Ann Van Eeckhaut, Birgitte Holst, Mette Marie Rosenkilde, Ilse Smolders, Steven Ballet
Neuromedin U (NMU) is a highly conserved endogenous peptide that is involved in a wide range of physiological processes such as regulation of feeding behavior, the stress response and nociception. The major limitation to use NMU as a therapeutic is its short half-life. Here, we describe the development of a set of novel NMU-analogs based on NMU-8, by introducing unnatural amino acids into the native sequence. This approach shows that it is possible to generate molecules with increased potency and improved plasma stability without major changes of the peptidic nature or the introduction of large conjugates...
December 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29327281/effect-of-early-natal-supplementation-of-paracetamol-on-attenuation-of-exotoxin-endotoxin-induced-pyrexia-and-precipitation-of-autistic-like-features-in-albino-rats
#20
Abdulaziz S Saeedan, Indu Singh, Mohd Nazam Ansari, Manjari Singh, Jitendra K Rawat, Uma Devi, Swetlana Gautam, Rajnish K Yadav, Gaurav Kaithwas
The present study was aimed to test the hypothesis that paracetamol (PCM) can precipitate autistic like features when used to counteract vaccine-induced fever using experimental rat pups. The pups were treated with measles mumps rubella (MMR) vaccine, diphtheria tetanus and pertussis (DPT) vaccines and lipopolysaccharide (LPS) with subsequent PCM treatment. The pups were evaluated for postnatal growth (weight gain, eye opening) and behavior alterations (swimming performance, olfactory discrimination, negative geotaxis, nociception, and locomotor activity) by performing battery of neurobehavioral test...
January 11, 2018: Inflammopharmacology
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