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https://www.readbyqxmd.com/read/29777135/n-methyl-d-aspartate-receptor-subtype-2b-antagonist-ro-25-6981-attenuates-neuropathic-pain-by-inhibiting-postsynaptic-density-95-expression
#1
Ling-Er Huang, Shao-Hui Guo, Lalita Thitiseranee, Yan Yang, Yan-Feng Zhou, Yong-Xing Yao
Postsynaptic density-95 (PSD-95) is a synaptic scaffolding protein that plays a crucial role in the development of neuropathic pain. However, the underlying mechanism remains unclear. To address the role of PSD-95 in N-methyl-D-aspartate receptor subtype 2B (NR2B) -mediated chronic pain, we investigated the relationship between PSD-95 activation and NR2B function in the spinal cord, by using a rat model of sciatic nerve chronic constriction injury (CCI). We demonstrate that the expression levels of total PSD-95 and cAMP response element binding protein (CREB), as well as phosphorylated NR2B, PSD-95, and CREB, in the spinal dorsal horn, and the interaction of NR2B with PSD-95 were increased in the CCI animals...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29774557/diabetes-induced-microvascular-complications-at-the-level-of-the-spinal-cord-a-contributing-factor-in-diabetic-neuropathic-pain
#2
N Ved, M E Da Vitoria Lobo, S M Bestall, C L Vidueira, N Beazley-Long, K Ballmer-Hofer, M Hirashima, D O Bates, L F Donaldson, R P Hulse
Abnormalities of neurovascular interactions within the central nervous system of diabetic patients is associated with the onset of many neurological disease states. However, to date, the link between the neurovascular network within the spinal cord and regulation of nociception has not been investigated despite neuropathic pain being common in diabetes. We hypothesised that hyperglycaemia-induced endothelial degeneration in the spinal cord, due to suppression of VEGF-A/VEGFR2 signalling, induces diabetic neuropathic pain...
May 17, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29773191/anti-inflammatory-and-antinociceptive-effects-of-2-2-dipyridyl-diselenide-through-reduction-of-inducible-nitric-oxide-synthase-nuclear-factor-kappa-b-and-c-jun-n-terminal-kinase-phosphorylation-levels-in-the-mouse-spinal-cord
#3
Suzan Gonçalves Rosa, César Augusto Brüning, Ana Paula Pesarico, Ana Cristina Guerra de Souza, Cristina Wayne Nogueira
Appropriate treatment of pain requires analgesics and anti-inflammatory drugs generally associated with undesirable side effects and not fully effective in a significant proportion of patients. Organoselenium compounds elicit a plenty of pharmacological effects in different animal models. Among these compounds, the 2,2`-dipyridyl diselenide (DPD) has a potent antioxidant effect and low toxicity. In this way, the aim of this study was to investigate the possible DPD antinociceptive effect and its mechanism of action, as well as the safety of the compound...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29768320/monocyte-chemoattractant-protein-1-as-a-predictor-of-coronary-atherosclerosis-in-patients-receiving-coronary-angiography
#4
Simon A Mahler, Thomas C Register, Robert F Riley, Ralph B D'Agostino, Jason P Stopyra, Chadwick D Miller
BACKGROUND: Animal studies suggest that monocyte chemoattractant protein-1 (MCP-1) is a promising biomarker for coronary artery atherosclerosis (CAA), but human studies have been inconclusive. OBJECTIVE: To determine potential relationships between plasma MCP-1 and CAA in patients with acute chest pain. METHODS: A secondary analysis of 150 patients enrolled in emergency department chest pain risk stratification clinical investigations was conducted...
June 2018: Critical Pathways in Cardiology
https://www.readbyqxmd.com/read/29764970/reinforcement-signaling-of-punishment-versus-relief-in-fruit-flies
#5
Christian König, Afshin Khalili, Mathangi Ganesan, Amrita P Nishu, Alejandra P Garza, Thomas Niewalda, Bertram Gerber, Yoshinori Aso, Ayse Yarali
Painful events establish opponent memories: cues that precede pain are remembered negatively, whereas cues that follow pain, thus coinciding with relief are recalled positively. How do individual reinforcement-signaling neurons contribute to this "timing-dependent valence-reversal?" We addressed this question using an optogenetic approach in the fruit fly. Two types of fly dopaminergic neuron, each comprising just one paired cell, indeed established learned avoidance of odors that preceded their photostimulation during training, and learned approach to odors that followed the photostimulation...
June 2018: Learning & Memory
https://www.readbyqxmd.com/read/29761734/functional-effects-of-trka-inhibition-on-system-x-c-mediated-glutamate-release-and-cancer-induced-bone-pain
#6
Tanya Miladinovic, Robert G Ungard, Katja Linher-Melville, Snezana Popovic, Gurmit Singh
Breast cancer cells release the signalling molecule glutamate via the system xC - antiporter, which is upregulated to exchange extracellular cystine for intracellular glutamate to protect against oxidative stress. Here, we demonstrate that this antiporter is functionally influenced by the actions of the neurotrophin nerve growth factor on its cognate receptor tyrosine kinase, TrkA, and that inhibiting this complex may reduce cancer-induced bone pain via its downstream actions on xCT, the functional subunit of system xC - ...
January 2018: Molecular Pain
https://www.readbyqxmd.com/read/29758584/inhibition-of-sympathetic-sprouting-in-ccd-rats-by-lacosamide
#7
Yuying Wang, Fuquan Huo
BACKGROUND: Early hyperexcitability activity of injured nerve/neuron is critical for developing sympathetic nerve sprouting within dorsal root ganglia (DRG). Since lacosamide (LCM), an anticonvulsant, inhibits Na+ channel. The present study tried to test the potential effect of LCM on inhibiting sympathetic sprouting in vivo. METHODS: LCM (50 mg/kg) was daily injected intraperitoneally into rats subjected to chronic compression DRG (CCD), an animal model of neuropathic pain that exhibits sympathetic nerve sprouting, for the 1st 7 days after injury...
May 14, 2018: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29756585/animal-models-used-for-testing-hydrogels-in-cartilage-regeneration
#8
Chuntie Zhu, Qiong Wu, Xu Zhang, Fubo Chen, Xiyang Liu, Qixiang Yang, Lei Zhu
Focal cartilage or osteochondral lesions can be painful and detrimental. Besides pain and limited function of joints, cartilage defect is considered as one of the leading extrinsic risk factors for osteoarthritis (OA). Thus, clinicians and scientists have paid great attention to regenerative therapeutic methods for the early treatment of cartilaginous defects. Regenerative medicine, showing great hope for regenerating cartilage tissue, rely on the combination of biodegradable scaffolds and specific biological cues, such as growth factors, adhesive factors and genetic materials...
May 14, 2018: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29756577/molecular-targets-and-natural-compounds-in-drug-development-for-the-treatment-of-inflammatory-pain
#9
Anna Woodbury, Myles R McCrary, Shan P Yu
This chapter explores therapeutic targets and the anti-inflammatory nature of some naturally-occurring compounds and the current or potential use of these compounds in the treatment of chronic inflammatory pain states. We will review the mechanisms of chronic inflammatory pain, the molecular targets of selected natural compounds in inhibiting inflammatory pain, and the traditional and current approaches to treating pain using these compounds. Previous research on experimental as well as clinical pain will be summarized from in vitro to animal and human models...
May 14, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29755988/bite-forces-and-their-measurement-in-dogs-and-cats
#10
REVIEW
Se Eun Kim, Boaz Arzi, Tanya C Garcia, Frank J M Verstraete
Bite force is generated by the interaction of the masticatory muscles, the mandibles and maxillae, the temporomandibular joints (TMJs), and the teeth. Several methods to measure bite forces in dogs and cats have been described. Direct in vivo measurement of a bite in dogs has been done; however, bite forces were highly variable due to animal volition, situation, or specific measurement technique. Bite force has been measured in vivo from anesthetized dogs by electrical stimulation of jaw adductor muscles, but this may not be reflective of volitional bite force during natural activity...
2018: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/29755555/the-ethanolic-extract-of-eysenhardtia-polystachya-ort-sarg-bark-and-its-fractions-delay-the-progression-of-rheumatoid-arthritis-and-show-antinociceptive-activity-in-murine-models
#11
Saudy Saret Pablo-Pérez, Benjamín Parada-Cruz, Olivier Christophe Barbier, María Estela Meléndez-Camargo
Eysenhardtia polystachya is widely used in folk medicine as an anti-rheumatic and analgesic agent, but no systematic study of its effects on several markers associated with rheumatoid arthritis and its ethnomedical use as analgesic agent has been performed. We evaluated the anti-arthritic and antinociceptive properties of an ethanolic extract of E. polystachya (EE) bark and its rich-flavonoids fractions in murine models. The EE was administered orally at doses of 25, 50, 100, and 200 mg/kg/day, and its fractions at 25 mg/kg/day in all animal models...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29752183/alkylsulfanyl-analogs-as-potent-%C3%AE-2-%C3%AE-ligands
#12
Kousei Shimada, Yasuo Ohata, Jun Kobayashi, Yoshiyuki Onishi, Asuka Kawamura, Yuki Domon, Naohisa Arakawa, Tatsuya Inoue, Yutaka Kitano, Fumihiko Matsuda, Yuki Abe, Tsuneo Deguchi
We identified novel (3R, 5S)-3-aminomethyl-5-methanesulfanyl hexanoic acid (5a: DS75091588) and (3R, 5S)-3-aminomethyl-5-ethanesulfanyl hexanoic acid (6a: DS18430756) as sulfur-containing γ-amino acid derivatives that were useful for the treatment of neuropathic pain. These two compounds exhibited a potent analgesic effect in animal models of both type I diabetes and type II diabetes, and good pharmacokinetics.
May 4, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29746088/structure-activity-studies-reveal-the-molecular-basis-for-gabab-receptor-mediated-inhibition-of-high-voltage-activated-calcium-channels-by-%C3%AE-conotoxin-vc1-1
#13
Mahsa Sadeghi, Bodil B Carstens, Brid P Callaghan, James T Daniel, Han Shen Tae, Tracey O'Donnell, Joel Castro, Stuart M Brierley, David J Adams, David J Craik, Richard J Clark
α-Conotoxins are disulfide-bonded peptides from cone snail venoms and are characterized by their affinity for nicotinic acetylcholine receptors (nAChR). Several α-conotoxins with distinct selectivity for nAChR subtypes have been identified as potent analgesics in animal models of chronic pain. However, a number of α-conotoxins have been shown to inhibit N-type calcium channel currents in rodent dissociated dorsal root ganglion (DRG) neurons via activation of G protein-coupled GABAB receptors (GABABR). Therefore it is unclear whether activation of GABABR or inhibition of α9α10 nAChRs is the analgesic mechanism...
May 10, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29745624/current-evidence-for-central-analgesic-effects-of-nsaids-an-overview-of-the-literature
#14
Pascal H Vuilleumier, Juerg Schliessbach, Michele Curatolo
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for a variety of painful conditions. Their peripheral anti-inflammatory effect due to inhibition of prostaglandin synthesis is well documented. In the late 1980ies, animal data suggested for the first time that NSAIDs might have central effects as well. Since that time, central inflammatory and nociceptive pathways that are potential targets of NSAIDs have been extensively studied in both animal and human models. This review provides an overview of the relevant literature implicated in the central effects of NSAIDs...
May 9, 2018: Minerva Anestesiologica
https://www.readbyqxmd.com/read/29745439/cannabinoids-and-gastrointestinal-motility-pharmacology-clinical-effects-and-potential-therapeutics-in-humans
#15
REVIEW
M Camilleri
BACKGROUND: Cannabinoid agents and cannabis are frequently used for relief of diverse gastrointestinal symptoms. PURPOSE: The objective of this article is to increase the awareness of gastroenterologists to the effects of cannabinoids on gastrointestinal motility, as gastroenterologists are likely to encounter patients who are taking cannabinoids, or those with dysmotility that may be associated with cannabinoid mechanisms. The non-selective cannabinoid agonist, dronabinol, retards gastric emptying and inhibits colonic tone and phasic pressure activity...
May 10, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29738922/behavioral-characteristics-of-capsaicin-mediated-cutaneous-myogenic-and-arthrogenic-orofacial-nociception-in-rats
#16
Eric L Rohrs, John K Neubert, Robert M Caudle, Kyle D Allen
OBJECTIVE: To assess changes in orofacial tactile sensitivity and gnawing related to capsaicin-mediated cutaneous, myogenic, and arthrogenic nociception in the rat. DESIGN: After recovery from anesthesia, orofacial tactile sensitivity and gnawing were assessed using operant testing methods following capsaicin application. Twenty female CD-Hairless rats were tested with bilateral capsaicin cream application to the cheek or with isoflurane anesthesia alone. Following several weeks of recovery, animals (n = 20) received either 10 μL unilateral masseter injections of vehicle, or phosphate buffered saline (PBS) to assess injection sensitization...
April 30, 2018: Archives of Oral Biology
https://www.readbyqxmd.com/read/29738803/standard-analgesics-reverse-burrowing-deficits-in-a-rat-cci-model-of-neuropathic-pain-but-not-in-models-of-type-1-and-type-2-diabetes-induced-neuropathic-pain
#17
Kris Rutten, Stacey A Gould, Luke Bryden, Henri Doods, Thomas Christoph, Anton Pekcec
BACKGROUND: Burrowing is a rodent behavior validated as a robust and reproducible outcome measure to infer the global effect of pain in several inflammatory pain models. However, less is known about the effect of analgesics on burrowing in neuropathic pain models and no studies have determined burrowing performance in models of diabetes-associated neuropathic pain. OBJECTIVE: To compare the sensitivity of the burrowing assay in different neuropathic pain models: mononeuropathic pain and diabetic polyneuropathy...
May 5, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29738554/repeated-mild-traumatic-brain-injury-can-cause-acute-neurologic-impairment-without-overt-structural-damage-in-juvenile-rats
#18
Alicia Meconi, Ryan C Wortman, David K Wright, Katie J Neale, Melissa Clarkson, Sandy R Shultz, Brian R Christie
Repeated concussion is becoming increasingly recognized as a serious public health concern around the world. Moreover, there is a greater awareness amongst health professionals of the potential for repeated pediatric concussions to detrimentally alter the structure and function of the developing brain. To better study this issue, we developed an awake closed head injury (ACHI) model that enabled repeated concussions to be performed reliably and reproducibly in juvenile rats. A neurological assessment protocol (NAP) score was generated immediately after each ACHI to help quantify the cumulative effects of repeated injury on level of consciousness, and basic motor and reflexive capacity...
2018: PloS One
https://www.readbyqxmd.com/read/29738328/persistent-postsurgical-pain-pathophysiology-and-preventative-pharmacologic-considerations
#19
Philippe Richebé, Xavier Capdevila, Cyril Rivat
The development of chronic pain is considered a major complication after surgery. Basic science research in animal models helps us understand the transition from acute to chronic pain by identifying the numerous molecular and cellular changes that occur in the peripheral and central nervous systems. It is now well recognized that inflammation and nerve injury lead to long-term synaptic plasticity that amplifies and also maintains pain signaling, a phenomenon referred to as pain sensitization. In the context of surgery in humans, pain sensitization is both responsible for an increase in postoperative pain via the expression of wound hyperalgesia and considered a critical factor for the development of persistent postsurgical pain...
May 7, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29736857/neuropathic-pain-after-spinal-cord-injury-challenges-and-research-perspectives
#20
REVIEW
Rani Shiao, Corinne A Lee-Kubli
Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that remains difficult to treat because underlying mechanisms are not yet fully understood. In part, this is due to limitations of evaluating neuropathic pain in animal models in general, and SCI rodents in particular. Though pain in patients is primarily spontaneous, with relatively few patients experiencing evoked pains, animal models of SCI pain have primarily relied upon evoked withdrawals. Greater use of operant tasks for evaluation of the affective dimension of pain in rodents is needed, but these tests have their own limitations such that additional studies of the relationship between evoked withdrawals and operant outcomes are recommended...
May 7, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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