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https://www.readbyqxmd.com/read/28820395/chemokine-c-x-c-motif-ligand-1-cxcl1-and-chemokine-c-x-c-motif-ligand-2-cxcl2-modulate-the-activity-of-trpv1-ib4-cultured-rat-dorsal-root-ganglia-neurons-upon-short-term-and-acute-application
#1
A F Deftu, A Filippi, K Shibsaki, R O Gheorghe, M Chiritoiu, V Ristoiu
CXCL1 and CXCL2 are two chemokines with 78% homology of their sequence. CXCL1 was associated with atopic dermatitis, a highly pruritic skin disease, but it is not clear what is its mechanism of action, while for CXCL2 there are no data about an association with itch sensitivity. CXCL1 and CXCL2 can modulate TRPV1 receptors, which are one of the most important downstream effectors for itch sensitivity, upon short-term (4 h) or long-term (24 h) incubation, but the data are incomplete. Therefore, the aims of this study were to better characterize the short-term effects of CXCL1 and CXCL2 on TRPV1(+)/IB4(+) dorsal root ganglia neurons known to include nociceptor and itch-sensitive neurons, and to obtain new data about the acute application (12 min) of the two chemokines on the same population of neurons...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28819330/synthesis-and-investigation-of-mixed-%C3%AE-opioid-and-%C3%AE-opioid-agonists-as-possible-bivalent-ligands-for-treatment-of-pain
#2
Ruben S Vardanyan, James P Cain, Saghar Mowlazadeh Haghighi, Vlad K Kumirov, Mary I McIntosh, Alexander J Sandweiss, Frank Porreca, Victor J Hruby
Several studies have suggested functional association between μ-opioid and δ-opioid receptors and showed that μ-activity could be modulated by δ-ligands. The general conclusion is that agonists for the δ-receptor can enhance the analgesic potency and efficacy of μ-agonists. Our preliminary investigations demonstrate that new bivalent ligands constructed from the μ-agonist fentanyl and the δ-agonist enkephalin-like peptides are promising entities for creation of new analgesics with reduced side effects for treatment of neuropathic pain...
March 2017: Journal of Heterocyclic Chemistry
https://www.readbyqxmd.com/read/28818462/discovery-of-non-zwitterionic-aryl-sulfonamides-as-nav1-7-inhibitors-with-efficacy-in-preclinical-behavioral-models-and-translational-measures-of-nociceptive-neuron-activation
#3
Yong-Jin Wu, Jason Guernon, Andrea McClure, Guanglin Luo, Ramkumar Rajamani, Alicia Ng, Amy Easton, Amy Newton, Clotilde Bourin, Dawn Parker, Kathleen Mosure, Omar Barnaby, Matthew G Soars, Ronald J Knox, Michele Matchett, Rick Pieschl, James Herrington, Ping Chen, D V Sivarao, Linda J Bristow, Nicholas A Meanwell, Joanne Bronson, Richard Olson, Lorin A Thompson, Carolyn Dzierba
Since zwitterionic benzenesulfonamide Nav1.7 inhibitors suffer from poor membrane permeability, we sought to eliminate this characteristic by replacing the basic moiety with non-basic bicyclic acetals and monocyclic ethers. These efforts led to the discovery of the non-zwitterionic aryl sulfonamide 49 as a selective Nav1.7 inhibitor with improved membrane permeability. Despite its moderate cellular activity, 49 exhibited robust efficacy in mouse models of neuropathic and inflammatory pain and modulated translational electromyogram measures associated with activation of nociceptive neurons...
August 9, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28817416/nicotinic-modulation-of-descending-pain-control-circuitry
#4
Iboro C Umana, Claire A Daniele, Brooke A Miller, Keith Gallagher, Meghan A Brown, Chandrika Abburi, Peggy Mason, Daniel S McGehee
Along with the well-known rewarding effects, activation of nicotinic acetylcholine receptors (nAChRs) can also relieve pain, and some nicotinic agonists have analgesic efficacy similar to opioids. A major target of analgesic drugs is the descending pain modulatory pathway, including the ventrolateral periaqueductal gray (vlPAG) and the rostral ventromedial medulla (RVM). Although activating nAChRs within this circuitry can be analgesic, little is known about the subunit composition and cellular effects of these receptors, particularly within the vlPAG...
July 3, 2017: Pain
https://www.readbyqxmd.com/read/28816506/inhibition-of-monoacylglycerol-lipase-another-signalling-pathway-for-potential-therapeutic-targets-in-migraine
#5
Rosaria Greco, Chiara Demartini, Anna Maria Zanaboni, Laura Berliocchi, Daniele Piomelli, Cristina Tassorelli
Background Drugs that modulate endocannabinoid signalling are effective in reducing nociception in animal models of pain and may be of value in the treatment of migraine. Methods We investigated the anti-nociceptive effects of inhibition of monoacylglycerol lipase (MGL), a key enzyme in the hydrolysis of the 2-arachidonoylglycerol, in a rat model of migraine based on nitroglycerin (NTG) administration. We evaluated c-fos expression in specific brain areas and nociceptive behavior in trigeminal and extra-trigeminal body areas...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28816296/-complete-androgen-insensitivity-syndrome-associated-with-vesical-fistula-a-case-report-and-literature-review
#6
K H Hua, L Yang, X W Zhang, W J Bai, Q Li, T Xu
Androgen insensitivity syndrome (AIS) is a very uncommon genetic disorder that results from the resistance of androgen receptor (AR) to androgen, which influences the formation of the male genitalia and in turn presents with female phenotype. Surgical resection of undesceaded testicle and different kinds of genitoplasty are crucial methods to correct the deformity of reproductive system, as well as hormone replacement therapy, which is an essential therapy for postoperational rehabilitation in AIS patients...
August 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28816177/electrical-stimulation-of-gut-motility-guided-by-an-in-silico-model
#7
Bradley Brigham Barth, Craig S Henriquez, Warren M Grill, Xiling Shen
OBJECTIVE: Neuromodulation of the central and peripheral nervous systems is becoming increasingly important for treating a diverse set of diseases-ranging from Parkinson's Disease and epilepsy to chronic pain. However, neuromodulation of the gastrointestinal (GI) tract has achieved relatively limited success in treating functional GI disorders, which affect a significant population, because the effects of stimulation on the enteric nervous system (ENS) and gut motility are not well understood...
August 17, 2017: Journal of Neural Engineering
https://www.readbyqxmd.com/read/28816143/radiation-therapy-versus-no-radiation-therapy-to-the-neo-breast-following-skin-sparing-mastectomy-and-immediate-autologous-free-flap-reconstruction-for-breast-cancer-patient-reported-and-surgical-outcomes-at-1-year-a-mastectomy-reconstruction-outcomes-consortium
#8
Andrew L Cooke, Julian Diaz-Abele, Tom Hayakawa, Ed Buchel, Kimberly Dalke, Pascal Lambert
PURPOSE: To determine whether adjuvant radiation therapy (RT) is associated with adverse patient-reported outcomes and surgical complications 1 year after skin-sparing mastectomy and immediate autologous free flap reconstruction for breast cancer. METHODS AND MATERIALS: We compared 24 domains of patient-reported outcome measures 1 year after autologous reconstruction between patients who received adjuvant RT and those who did not. A total of 125 patients who underwent surgery between 2012 and 2015 at our institution were included from the Mastectomy Reconstruction Outcomes Consortium study database...
September 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28814928/love-as-a-modulator-of-pain
#9
REVIEW
Sofina Tamam, Asma Hayati Ahmad
Pain is modulated by various factors, the most notable of which is emotions. Since love is an emotion, it can also modulate pain. The answer to the question of whether it enhances or reduces pain needs to be determined. A review was conducted of animal and human studies in which this enigmatic emotion and its interaction with pain was explored. Recent advances in neuroimaging have revealed similarities in brain activation relating to love and pain. At the simplest level, this interaction can be explained by the overlapping network structure in brain functional connectivity, although the explanation is considerably more complex...
May 2017: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/28814894/startle-modulation-by-heat-pain-with-varying-threat-levels-in-chronic-pain-patients-and-pain-free-controls
#10
C Horn-Hofmann, D Wolf, S Wolff, M Heesen, K Knippenberg-Bigge, P M Lang, S Lautenbacher
BACKGROUND: Empirical evidence suggests that affective responses to pain are changed in chronic pain. The investigation of startle responses to pain might contribute to clarifying whether such alterations also expand to motivational defensive reactions. We aimed at comparing startle responses to tonic heat pain with high threat (HT) or low threat (LT) in patients with chronic musculoskeletal pain and controls. As pain-related anxiety and catastrophizing are typically elevated in chronic pain, we expected to find stronger startle responses in patients specifically under experimental HT...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28814817/conjugated-polymers-mediate-effective-activation-of-the-mammalian-ion-channel-transient-receptor-potential-vanilloid-1
#11
F Lodola, N Martino, G Tullii, G Lanzani, M R Antognazza
Selective and rapid regulation of ionic channels is pivotal to the understanding of physiological processes and has a crucial impact in developing novel therapeutic strategies. Transient Receptor Potential (TRP) channels are emerging as essential cellular switches that allow animals to respond to their environment. In particular, the Vanilloid Receptor 1 (TRPV1), besides being involved in the body temperature regulation and in the response to pain, has important roles in several neuronal functions, as cytoskeleton dynamics, injured neurons regeneration, synaptic plasticity...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814476/phase-i-trial-of-the-androgen-receptor-modulator-cr1447-in-breast-cancer
#12
Martin Zweifel, Beat Thuerlimann, Salome Riniker, Patrik Weder, Roger von Moos, Olivia Pagani, Martin Bigler, Karin M Rothgiesser, Christiane Pilop, Hanne Hawle, Peter Brauchli, Coya Tapia, Wolfgang Schoenfeld, Cristiana Sessa
CR 1447 (4-hydroxytestosterone, 4-OHT) binds to the androgen receptor and has antiproliferative activity in both ER-positive and ER-negative/AR-positive breast cancer cells in pre-clinical studies. The objective of this first-in man trial was to evaluate safety and to determine the dose of CR1447, administered as an ointment, for Phase II. Escalating doses (100, 200, 400 mg) of CR1447 were administered topically on a daily basis to patients with ER-positive/AR-positive/HER2-negative advanced breast cancer pretreated with several lines of therapy...
August 16, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28814263/acute-pain-management-in-hospitalized-children
#13
Ria Dancel, Edmund Allen Liles, Darren Fiore
BACKGROUND: Acute pain in hospitalized pediatric patients is prevalent. Recent shifts in the paradigm of pediatric acute pain management focus less on reliance on opioids, due to their adverse side effects and risk of dependence, and more on multimodal pain management. OBJECTIVE: We sought to review the most recent studies on acute pain management in hospitalized pediatric patients. METHODS: We searched the Cochrane Database and PubMed for articles published in the past five years regarding the treatment of acute pain in pediatric patients focusing on large randomized or quasi-randomized control trials, cohort trials, and meta-analyses...
August 16, 2017: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/28814122/flibanserin-toxicity-in-a-toddler-following-ingestion
#14
Nicholas Granzella, Betty C Chen, Geoffrey S Baird, Matthew Valento
INTRODUCTION: Flibanserin is a medication recently approved by the FDA for treatment of generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Its mechanism of action is not fully understood but is thought to modulate serotonin receptors and increase levels of norepinephrine and dopamine. While much is known about toxicity of other drugs which affect these systems, there is little information about toxicity of flibanserin at this time. CASE: We present a case of a 2-year-old boy who ingested an estimated 600 mg of his mother's flibanserin...
August 17, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28812392/psychometric-properties-of-the-performing-arts-module-of-the-disabilities-of-the-arm-shoulder-and-hand-questionnaire
#15
Vera Baadjou, Rob de Bie, Christine Guptill, Rob Smeets
BACKGROUND: The Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) offers an optional performing arts module. The goal was to examine the psychometric properties of this module in musicians. METHODS: This study is a secondary analysis of a randomized controlled trial on the effectiveness of a biopsychosocial intervention to prevent or reduce playing-related disability in conservatory students. Baseline data were used to examine internal consistency and discriminative validity of the performing arts module of the DASH questionnaire...
August 16, 2017: Disability and Rehabilitation
https://www.readbyqxmd.com/read/28811623/immune-dysregulation-in-patients-with-carpal-tunnel-syndrome
#16
Gila Moalem-Taylor, Benny Baharuddin, Barbara Bennett, Arun V Krishnan, William Huynh, Matthew C Kiernan, Cindy Shin-Yi Lin, Boaz Shulruf, Elizabeth Keoshkerian, Barbara Cameron, Andrew Lloyd
Peripheral immunity plays a key role in maintaining homeostasis and conferring crucial neuroprotective effects on the injured nervous system, while at the same time may contribute to increased vulnerability to neuropathic pain. Little is known about the reciprocal relationship between entrapment neuropathy and peripheral immunity. This study investigated immune profile in patients with carpal tunnel syndrome (CTS), the most prevalent entrapment neuropathy. All patients exhibited neurophysiological abnormalities in the median nerve, with the majority reporting neuropathic pain symptoms...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28809765/cyclin-dependent-kinase-5-modulates-the-p2x2a-receptor-channel-gating-through-phosphorylation-of-c-terminal-threonine-372
#17
Claudio Coddou, Rodrigo Sandoval, Patricio Castro, Pablo Lazcano, Maria José Hevia, Milos Rokic, Bradford Hall, Anita Terse, Christian Gonzalez-Billault, Ashok B Kulkarni, Stanko S Stojilkovic, Elias Utreras
The purinergic P2X2 receptor (P2X2R) is an adenosine triphosphate-gated ion channel widely expressed in the nervous system. Here, we identified a putative cyclin-dependent kinase 5 (Cdk5) phosphorylation site in the full-size variant P2X2aR (TPKH), which is absent in the splice variant P2X2bR. We therefore investigated the effects of Cdk5 and its neuronal activator, p35, on P2X2aR function. We found an interaction between P2X2aR and Cdk5/p35 by co-immunofluorescence and co-immunoprecipitation in HEK293 cells...
July 17, 2017: Pain
https://www.readbyqxmd.com/read/28809421/-reactive-nano-complex-coated-medical-cotton-a-facile-avenue-for-tailored-release-of-small-molecules
#18
Adil Majeed Rather, Sulendar Mahato, Kousik Maji, Neeha Gogoi, Uttam Manna
Controlled and sustained release of drug-like small molecules in an aqueous medium still remains a challenging problem due to rapid infiltration of liquid water in most reported drug release systems. However, internal-superhydrophobicity with an antifouling property extending beyond the surface of a material recently has been recognized as a potential avenue for sustained and extended release of drug-like small molecules. Sluggish removal of metastable trapped air in a superhyrophobic material provides a basis to achieve extended release of encapsulated small molecules...
August 15, 2017: Nanoscale
https://www.readbyqxmd.com/read/28809075/allosteric-modulation-of-%C3%AE-4%C3%AE-2-nicotinic-acetylcholine-receptors-desformylflustrabromine-potentiates-antiallodynic-response-of-nicotine-in-a-mouse-model-of-neuropathic-pain
#19
D Bagdas, D Ergun, A Jackson, W Toma, M K Schulte, M I Damaj
BACKGROUND: Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels. The α4β2 subtype of nAChRs plays an important role in the mediation of pain and several nicotine-evoked responses. Agonists and partial agonists of α4β2 nAChRs show efficacy in animal pain models. In addition, the antinociceptive properties of nicotine, a non-selective nAChR agonist with a high affinity for α4β2 nAChRs, is well-known. There is a growing body of evidence pointing to allosteric modulation of nAChRs as an alternative treatment strategy in experimental pain...
August 14, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28808583/successful-spinal-cord-stimulation-for-neuropathic-below-level-spinal-cord-injury-pain-following-complete-paraplegia-a-case-report
#20
Tim A Reck, Gunther Landmann
INTRODUCTION: Neuropathic pain is common in patients with spinal cord injury (SCI) and often difficult to treat. We report a case where epidural spinal cord stimulation (SCS) below the level of injury has been successfully applied in a patient with a complete spinal cord lesion. CASE PRESENTATION: A 53-year-old female presented with neuropathic below-level SCI pain of both lower legs and feet due to complete SCI below T5. Time and pain duration since injury was 2 years...
2017: Spinal Cord Series and Cases
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