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https://www.readbyqxmd.com/read/29028747/nervous-system-delivery-of-antilysophosphatidic-acid-antibody-by-nasal-application-attenuates-mechanical-allodynia-after-traumatic-brain-injury-in-rats
#1
Andreas Eisenried, Anders C N Meidahl, Michael Klukinov, Alexander Z Tzabazis, Roger A Sabbadini, J David Clark, David C Yeomans
Lysophosphatidic acid (LPA) is a bioactive lipid that impacts neurological outcomes after neurotrauma by inhibiting neuroregeneration, promoting inflammation, and contributing to behavioral deficits. Blocking LPA signaling with a novel anti-LPA monoclonal antibody (mAb) is neuroprotective after traumatic brain injury (TBI) if given to injured animals whose blood-brain barrier (BBB) has been compromised. It is hypothesized that the anti-LPA mAb could improve chronic pain initiated by TBI. However, poor brain penetration after systemic application of the antibody makes access to the central nervous system (CNS) problematic in situations where the BBB is intact...
November 2017: Pain
https://www.readbyqxmd.com/read/29028074/efficacy-and-safety-of-5-lidocaine-medicated-plasters-in-localized-pain-with-neuropathic-and-or-inflammatory-characteristics-an-observational-real-world-study
#2
F Amato, G Duse, L Consoletti, C Lo Presti, V Firetto, G Ciliberto, L A Parigi, V Palmieri, M Mazza
OBJECTIVE: Based on clinical study results, 5% lidocaine-medicated plaster (5% LMP) is currently recommended for the treatment of localized peripheral neuropathic pain, such as post-herpetic neuralgia (PHN). However, its effective action, as well as the high safety, have indeed led to its use in clinical practice for pain conditions with similar pathophysiological mechanisms. In this study, the efficacy and safety of 5% LMP were investigated in patients with localized pain with neuropathic and/or inflammatory characteristics, such as PHN, post-traumatic/surgical or musculoskeletal pain...
September 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29025860/negative-regulation-of-trpa1-by-amp-activated-protein-kinase-in-primary-sensory-neurons-as-a-potential-mechanism-of-painful-diabetic-neuropathy
#3
Shenglan Wang, Kimiko Kobayashi, Yoko Kogure, Hiroki Yamanaka, Satoshi Yamamoto, Hideshi Yagi, Koichi Noguchi, Yi Dai
AMP activated protein kinase (AMPK) is a widely expressed intracellular energy sensor that monitors and modulates energy expenditure. Transient receptor potential ankyrin 1 (TRPA1) channel is a widely recognized chemical and thermal sensor that plays vital roles in pain transduction. Here, we discovered a functional link between AMPK and TRPA1 in dorsal root ganglion (DRG) neurons, in which AMPK activation rapidly resulted in downregulation of membrane-associated TRPA1 and its channel activity within minutes...
October 12, 2017: Diabetes
https://www.readbyqxmd.com/read/29022756/soluble-guanylyl-cyclase-is-a-critical-regulator-of-migraine-associated-pain
#4
Manel Ben Aissa, Alycia F Tipton, Zachariah Bertels, Ronak Gandhi, Laura S Moye, Madeline Novack, Brian M Bennett, Yueting Wang, Vladislav Litosh, Sue H Lee, Irina N Gaisina, Gregory Rj Thatcher, Amynah A Pradhan
Background Nitric oxide (NO) has been heavily implicated in migraine. Nitroglycerin is a prototypic NO-donor, and triggers migraine in humans. However, nitroglycerin also induces oxidative/nitrosative stress and is a source of peroxynitrite - factors previously linked with migraine etiology. Soluble guanylyl cyclase (sGC) is the high affinity NO receptor in the body, and the aim of this study was to identify the precise role of sGC in acute and chronic migraine. Methods We developed a novel brain-bioavailable sGC stimulator (VL-102), and tested its hyperalgesic properties in mice...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29017971/induction-of-suppressor-of-cytokine-signaling-3-via-hsf-1-hsp70-tlr4-axis-attenuates-neuroinflammation-and-ameliorates-postoperative-pain
#5
Yi-Xin Fan, Cheng Qian, Bingqian Liu, Chaoyu Wang, Haijiao Liu, Xiuxiu Pan, Peng Teng, Liang Hu, Guangqin Zhang, Yuan Han, Mi Yang, Xue-Feng Wu, Wen-Tao Liu
Postoperative pain is a common form of acute pain that, if not managed effectively, can become chronic pain. Evidence has shown that glia, especially microglia, mediate neuroinflammation, which plays a vital role in pain sensitization. Moreover, toll-like receptor 4 (TLR4), the tumor necrosis factor receptor (TNF-R), the interleukin-1 receptor (IL-1R), and the interleukin-6 receptor (IL-6R) have been considered key components in central pain sensitization and neuroinflammation. Therefore, we hypothesized that activation of the body's endogenous "immune brakes" will inhibit these receptors and achieve inflammation tolerance as well as relieve postoperative pain...
October 7, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29017758/in-vitro-and-in-vivo-pharmacological-characterization-of-asp8477-a-novel-highly-selective-fatty-acid-amide-hydrolase-inhibitor
#6
Tomonari Watabiki, Noriko Tsuji, Tetsuo Kiso, Tohru Ozawa, Fumie Narazaki, Shuichiro Kakimoto
Although exogenous agonists for cannabinoid (CB) receptors are clinically effective for treating chronic pain, global activation of brain CB receptors causes frequent central nervous system (CNS) side-effects. Fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme for anandamide (AEA), an endogenous CB. Recently, we discovered a novel FAAH inhibitor, 3-pyridyl 4-(phenylcarbamoyl)piperidine-1-carboxylate (ASP8477). In vitro studies demonstrated that ASP8477 inhibited human FAAH-1, FAAH-1 (P129T) and FAAH-2 activity with IC50 values of 3...
October 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29017199/-ciguatera-or-why-you-should-enquire-about-fish-consumption-in-cases-of-cold-allodynia
#7
Miriam Friedemann, Claus Doberauer, Gereon R Fink, Lothar Burghaus
Ciguatoxine sind potente, von Mikroalgen produzierte, marine Biotoxine, die sich in tropischen Raubfischen, lokal und saisonal unterschiedlich stark, anreichern können. Kurze Zeit nach dem Fischverzehr treten gastrointestinale, neurologische und/oder kardiovaskuläre Vergiftungssymptome auf. Durch die hohe Affinität der Toxine zu neuronalen Natriumkanälen sind neurologische Symptome für Ciguatera-Vergiftungen charakteristisch. Nahezu pathognomonisch ist dabei die Kälteallodynie, bei der kalte Oberflächen als heiß, schmerzhaft oder extrem unangenehm empfunden werden...
October 2017: Fortschritte der Neurologie-Psychiatrie
https://www.readbyqxmd.com/read/29016952/migraine-does-not-affect-pain-intensity-perception-a-cross-sectional-study
#8
Antonio Russo, Alessandro Tessitore, Antonio Bruno, Mattia Siciliano, Laura Marcuccio, Marcello Silvestro, Gioacchino Tedeschi
Objective: To explore perceived pain intensity (PPI) in three drug-naïve patient groups characterized by homogeneous migraine phenotypes-migraine without aura without cutaneous allodynia (MwoA CA-), MwoA with ictal CA (MwoA CA+), and migraine with aura without cutaneous allodynia (MwA CA-)-compared with age- and sex-matched healthy controls (HCs). Methods: Using trigeminal heat stimulation (THS) at three different predefined intensities (41 °C, 51 °C, and 53 °C) performed by the contact heat-evoked potential stimulator (CHEPS), PPI was investigated in 34 patients with MwoA CA-, 30 patients with MwoA CA+, and 30 patients with MwA CA- compared with 30 age- and sex-matched HCs...
July 28, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28993838/delta-opioid-receptor-expression-and-function-in-primary-afferent-somatosensory-neurons
#9
Amaury François, Grégory Scherrer
The functional diversity of primary afferent neurons of the dorsal root ganglia (DRG) generates a variety of qualitatively and quantitatively distinct somatosensory experiences, from shooting pain to pleasant touch. In recent years, the identification of dozens of genetic markers specifically expressed by subpopulations of DRG neurons has dramatically improved our understanding of this diversity and provided the tools to manipulate their activity and uncover their molecular identity and function. Opioid receptors have long been known to be expressed by discrete populations of DRG neurons, in which they regulate cell excitability and neurotransmitter release...
October 10, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28987074/combination-of-rheum-ribes-and-metformin-against-diabetes-thermal-hyperalgesia-and-tactile-allodynia-in-a-mice-model
#10
Karim Raafat, Abdalla El-Lakany
Context • The prevalence of diabetes mellitus (DM) is increasing. Because of its progressive nature, therapeutic shifts and combinations are often required to reduce the risk of glucose toxicity and avoid serious side effects. To treat DM and its related complications, a combination therapy may offer a promising remedy to counteract those issues. Objectives • The study was established to evaluate the phytochemical content of a standardized aqueous extract of Rheum ribes (RR) and to determine the antidiabetic, antihyperalgesic, and antimechanical allodynic effects of 50 mg/kg of RR alone, 25 mg/kg of metformin (MTF) alone, and a combination of the 2 substances (MTF+RR) in mice with alloxan-induced diabetes...
October 2, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28984399/characterization-of-a-novel-capsaicin-heat-ongoing-pain-model
#11
R C Price, W Gandhi, C Nadeau, R Tarnavskiy, A Qu, E Fahey, L Stone, P Schweinhardt
BACKGROUND: Human experimental pain models provide an important translational link between pre-clinical models and clinical pain. Using topical capsaicin and continuous heat application, the novel capsaicin/heat ongoing pain (CHOP) model induces long-lasting experimental pain of which the perceived intensity can be individually adjusted. METHODS: In the CHOP model, capsaicin or control cream is applied to a 10 × 10 cm skin area and a heating pad is applied over the area after cream removal...
October 6, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28982597/chronic-trans-astaxanthin-treatment-exerts-antihyperalgesic-effect-and-corrects-co-morbid-depressive-like-behaviors-in-mice-with-chronic-pain
#12
Xi Jiang, Qizhi Yan, Fuhe Liu, Changfeng Jing, Lianshu Ding, Lijin Zhang, Cong Pang
Patients suffering from chronic neuropathic pain are at high risk of co-morbid depression, which burdens healthcare. Trans-astaxanthin has been shown in our previous studies to exert antidepressant-like effect. This work aimed to investigate the effects of trans-astaxanthin on pain-related depressive-like behaviors in mice and explored the mechanism(s). Chronic constriction injury (CCI) model was used in this research. Chronic pain was evaluated by thermal hyperalgesia in Hargreaves test and mechanical allodynia in von Frey test, depressive-like behaviors were evaluated by immobility time in forced swim test and tail suspension test...
October 2, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28979159/sound-stress-induced-altered-nociceptive-behaviors-are-associated-with-increased-spinal-crfr2-gene-expression-in-a-rat-model-of-burn-injury
#13
Natasha M Sosanya, Alex V Trevino, Roger L Chavez, Robert J Christy, Bopaiah P Cheppudira
Sound stress (SS) elicits behavioral changes, including pain behaviors. However, the neuronal mechanisms underlying SS-induced pain behaviors remain to be explored. The current study examined the effects of SS on nociceptive behaviors and changes in expression of the spinal corticotropin-releasing factor (CRF) system in male Sprague Dawley rats with and without thermal pain. We also studied the effects of SS on plasma corticosterone and fecal output. Rats were exposed to 3 days of SS protocol (n = 12/group)...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28976002/structural-co-variance-patterns-in-migraine-a-cross-sectional-study-exploring-the-role-of-the-hippocampus
#14
Catherine D Chong, Gina M Dumkrieger, Todd J Schwedt
OBJECTIVE: To interrogate hippocampal morphology and structural co-variance patterns in migraine patients and to investigate whether structural co-variance patterns relate to migraine disease characteristics. BACKGROUND: Migraine is associated with structural alterations in widespread cortical and subcortical regions associated with the sensory, cognitive, and affective components of pain processing. Recent studies have shown that migraine patients have differences in hippocampal structure and function relative to healthy control subjects, but whether hippocampal structure relates to disease characteristics including frequency of attacks, years lived with migraine and symptoms of allodynia remains unknown...
October 4, 2017: Headache
https://www.readbyqxmd.com/read/28974374/the-role-of-sex-in-sleep-deprivation-related-changes-of-nociception-and-conditioned-pain-modulation
#15
Nicole Eichhorn, Rolf-Detlef Treede, Sigrid Schuh-Hofer
Sex matters both in the clinical field of pain and sleep medicine. Sleep disturbances are highly prevalent in chronic pain patients and have been shown to deteriorate the pain condition. The pathomechanisms by which insomnia aggravates pain are currently unknown. Descending pain control may be compromised by disturbed sleep, but respective studies are few, inconsistent and largely imbalanced with respect to sex. We studied the role of sex on the effect of sleep deprivation on endogenous pain modulation and on nociceptive thresholds in a highly homogenous study population of 18 female (23...
October 1, 2017: Neuroscience
https://www.readbyqxmd.com/read/28974100/neuronal-dysexcitability-may-be-a-biomarker-of-migraine-a-visual-evoked-potential-study
#16
Jayantee Kalita, Ravi Uniyal, Usha K Misra, Sanjeev K Bhoi
We report neuronal sensitization and impaired habituation in migraine using pattern reversal visual evoked potential (PRVEP) and correlate these with clinical characteristics of migraine. Sixty-five migraineurs and 30 healthy controls were included. A detailed clinical examination was done and migraine characteristics, including migraine trigger, photophobia, phonophobia, and allodynia were noted. Consecutive 5 blocks of PRVEP were recorded averaging 100 epochs at 3 Hz stimuli. The amplitude of N75 and P100 were measured...
September 1, 2017: Clinical EEG and Neuroscience: Official Journal of the EEG and Clinical Neuroscience Society (ENCS)
https://www.readbyqxmd.com/read/28972650/characterisation-of-a-rat-model-of-bortezomib-induced-painful-neuropathy
#17
Natalie A Duggett, Sarah J L Flatters
BACKGROUND: Bortezomib (Velcade®) is a breakthrough treatment for multiple myeloma, significantly improving patient survival. However, its use is limited by painful neuropathy often resulting in dose reduction/cessation of first-line treatment due to lack of treatment. The aim of this study was to characterise a clinically-relevant rat model of bortezomib-induced painful neuropathy, using established evoked measures and novel ethological techniques, to aid drug discovery. EXPERIMENTAL APPROACH: Adult male Sprague-Dawley rats were injected intraperitoneally (i...
October 3, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28971699/cgrp-receptor-antagonist-mk-8825-attenuates-cortical-spreading-depression-induced-pain-behavior
#18
Aslı Filiz, Nermin Tepe, Sajedeh Eftekhari, H Evren Boran, Ergin Dilekoz, Lars Edvinsson, Hayrunnisa Bolay
Background and objective The present study aimed to investigate the effects of selective calcitonin gene related peptide (CGRP) receptor antagonist (MK-8825) on cortical spreading depression (CSD) induced pain behavior and anxiety in freely-moving rats, and neuronal activation in the correlated anatomical regions. Methods CSD was induced while keeping all meningeal layers and BBB intact and MK-8825 was administered in two different doses. Regional cerebral blood flow (rCBF), arterial pressure and DC shift were recorded...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28970572/schwann-cells-promote-post-traumatic-nerve-inflammation-and-neuropathic-pain-through-mhc-class-ii
#19
Maike Hartlehnert, Angelika Derksen, Tim Hagenacker, David Kindermann, Maria Schäfers, Mathias Pawlak, Bernd C Kieseier, Gerd Meyer Zu Horste
The activation of T helper cells requires antigens to be exposed on the surface of antigen presenting cells (APCs) via MHC class II (MHC-II) molecules. Expression of MHC-II is generally limited to professional APCs, but other cell types can express MHC-II under inflammatory conditions. However, the importance of these conditional APCs is unknown. We and others have previously shown that Schwann cells are potentially conditional APCs, but the functional relevance of MHC-II expression by Schwann cells has not been studied in vivo...
October 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28970359/investigation-of-diacylglycerol-lipase-alpha-inhibition-in-the-mouse-lipopolysaccharide-inflammatory-pain-model
#20
Jenny L Wilkerson, Giulia Donvito, Travis W Grim, Rehab A Abdullah, Daisuke Ogasawara, Benjamin F Cravatt, Aron H Lichtman
Diacylglycerol lipase (DAGL) α and β, the major biosynthetic enzymes of the endogenous cannabinoid (endocannabinoid) 2-arachidonylglycerol (2-AG), are highly expressed in the nervous system and immune system, respectively. Genetic deletion or pharmacological inhibition of DAGL-β protects against lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages, and reverses LPS-induced allodynia in mice. In order to gain insight into the contribution of DAGL-α in LPS-induced allodynia, we tested global knockout mice as well as DO34, a dual DAGL-α/-β inhibitor...
October 2, 2017: Journal of Pharmacology and Experimental Therapeutics
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