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Central sensitisation

Iglika G Ivanova, Catherine V Park, Adrian I Yemm, Niall S Kenneth
HIF1α (hypoxia inducible factor 1α) is the central regulator of the cellular response to low oxygen and its activity is deregulated in multiple human pathologies. Consequently, given the importance of HIF signaling in disease, there is considerable interest in developing strategies to modulate HIF1α activity and down-stream signaling events. In the present study we find that under hypoxic conditions, activation of the PERK branch of the unfolded protein response (UPR) can suppress the levels and activity of HIF1α by preventing efficient HIF1α translation...
February 26, 2018: Nucleic Acids Research
Vanessa Garcia-Larsen, Despo Ierodiakonou, Katharine Jarrold, Sergio Cunha, Jennifer Chivinge, Zoe Robinson, Natalie Geoghegan, Alisha Ruparelia, Pooja Devani, Marialena Trivella, Jo Leonardi-Bee, Robert J Boyle
BACKGROUND: There is uncertainty about the influence of diet during pregnancy and infancy on a child's immune development. We assessed whether variations in maternal or infant diet can influence risk of allergic or autoimmune disease. METHODS AND FINDINGS: Two authors selected studies, extracted data, and assessed risk of bias. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess certainty of findings. We searched Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), Web of Science, Central Register of Controlled Trials (CENTRAL), and Literatura Latino Americana em Ciências da Saúde (LILACS) between January 1946 and July 2013 for observational studies and until December 2017 for intervention studies that evaluated the relationship between diet during pregnancy, lactation, or the first year of life and future risk of allergic or autoimmune disease...
February 2018: PLoS Medicine
Shelley Gorman, Sian Geldenhuys, Clare E Weeden, Michele A Grimbaldeston, Prue H Hart
Topical application of biologically active vitamin D [1,25-dihydroxyvitamin D (1,25(OH)2D)], or low-calcemic analogues, curb skin inflammation through mechanisms that involve migratory dendritic cells (DCs) and regulatory T (TReg) cells. 1,25(OH)2D also promotes immunoregulation by mast cells, and inhibits the development of T helper type-9 (Th9) cells that secrete interleukin-9 (IL-9). Here, we investigated the ability of topical 1,25(OH)2D to suppress contact dermatitis through an IL-9-dependent process, examining mast cells and IL-9-secreting T cells...
February 1, 2018: Archives of Dermatological Research
Richard T Amison, Simon Cleary, Yanira Riffo-Vasquez, Maidda Bajwa, Clive P Page, Simon C Pitchford
BACKGROUND: Platelet activation occurs in patients with allergic inflammation, and platelets can be activated directly by allergen via an IgE-dependent process. Platelets activate antigen-presenting cells (APCs) such as CD11c+ dendritic cells (DCs) in vitro. Whilst CD11c+ DCs are requisite for allergen sensitization, the role of platelets in this process is unknown. OBJECTIVES: We investigated whether platelets were necessary for allergen sensitization. METHODS: Balb/c mice sensitised to ovalbumin (OVA), were exposed to subsequent aerosolized allergen (OVA challenge)...
January 24, 2018: American Journal of Respiratory Cell and Molecular Biology
Carmen Aguirre-Hernández, Héctor Maya-Pineda, Julia San Millán, Y K Stella Man, Yong-Jie Lu, Gunnel Halldén
Anti-apoptotic Bcl-2 is frequently activated in human malignant cells to promote cell survival and inhibit cell death. Replication-selective oncolytic adenoviruses deleted in the functional Bcl-2 homologue E1B19K potently synergise with apoptosis-inducing chemotherapeutic drugs, including mitoxantrone for prostate cancer. Here, we demonstrate that our previously generated oncolytic mutant Ad∆∆ (E1B19K- and E1ACR2-deleted) caused potent synergistic apoptotic cell death in both drug-sensitive 22Rv1, and drug-insensitive PC3 and PC3M prostate cancer cells...
January 24, 2018: Oncogenesis
J A Pijpers, N J Wiendels, H Koppen, M D Ferrari, J Haan, G M Terwindt
- Medication-overuse headache is a highly prevalent disorder with a major impact on the quality of life.- Medication-overuse headache is defined as headache on ≥ 15 days per month with overuse of acute headache medication for ≥ 3 months. We talk about overuse in case of intake of simple analgesics on ≥ 15 days per month or triptans or combinations of analgesics on ≥ 10 days per month.- The underlying type of headache is usually migraine or tension-type headache.- One of the possible underlying mechanisms of medication-overuse headache is changed sensitivity as a consequence of central sensitisation...
2018: Nederlands Tijdschrift Voor Geneeskunde
Esther Ha Sim, Ian A Yang, Richard Wood-Baker, Rayleen V Bowman, Kwun M Fong
BACKGROUND: The role of gefitinib for the treatment of advanced non-small cell lung cancer (NSCLC) is evolving. We undertook a systematic review to evaluate the available evidence from all randomised trials. OBJECTIVES: To determine the effectiveness and safety of gefitinib as first-line, second-line or maintenance treatment for advanced NSCLC. SEARCH METHODS: We performed searches in CENTRAL, MEDLINE and Embase from inception to 17 February 2017...
January 16, 2018: Cochrane Database of Systematic Reviews
Changfeng Lu, Xun Sun, Chong Wang, Yu Wang, Jiang Peng
A painful neuroma is a common complication of a peripheral nerve injury or amputation, and it can cause tremendous pain that is resistant to most analgesics. Furthermore, painful neuromas have a high postoperative recurrence rate. Painful neuromas are often accompanied by functional disorders, drastically reducing the patient's quality of life. Several pathophysiological mechanisms have been proposed to explain this type of neuropathic pain, including peripheral and central sensitisation and the involvement of nerve growth factor, α-smooth muscle actin, the cannabinoid CB2 receptor and structural changes in neuroma fibres...
January 8, 2018: Reviews in the Neurosciences
Wietske Rienstra, Tim Blikman, Baukje Dijkstra, Jos van Raay, Geranda Slager, Sjoerd Bulstra, Martin Stevens, Inge van den Akker-Scheek
BACKGROUND: The modified painDETECT questionnaire (PDQ) is a self-reported questionnaire to discriminate between nociceptive and neuropathic-like pain in patients with knee/hip osteoarthritis (OA). This study aims to assess the structural and construct validity of this questionnaire. METHODS: Confirmatory factor analysis and hypothesis-testing was used. For 168 patients, predefined hypotheses were formulated on the correlation between the modified painDETECT and several other questionnaires, and in a subsample of 46 with pain pressure thresholds (PPTs)...
December 8, 2017: Disability and Rehabilitation
Michael Skovdal Rathleff, Camilla Rams Rathleff, Aoife Stephenson, Rebecca Mellor, Mark Matthews, Kay Crossley, Bill Vicenzino
Patellofemoral Pain (PFP) is highly prevalent among adults and adolescents. Localized mechanical hyperalgesia around the knee and tibialis anterior have been observed in people with PFP, but limited knowledge of potential manifestations of central sensitisation exists. The aims of this study were to study conditioned pain modulation (CPM) and wide-spread hyperalgesia in adults with PFP. This assessor-blinded cross-sectional study design compared CPM and mechanical pressure pain thresholds (PPT) between 33 adults (23 females) diagnosed with PFP and 32 age and sex matched pain-free controls...
2017: PloS One
Jia Liu, Lu-Ning Wang
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. This is an update of a review first published in January 2014 and subsequently updated in October 2015. OBJECTIVES: To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA)...
December 2, 2017: Cochrane Database of Systematic Reviews
Lara C Morley, Thomas Tang, Ephia Yasmin, Robert J Norman, Adam H Balen
BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by infrequent or absent ovulation, and high levels of androgens and insulin (hyperinsulinaemia). Hyperinsulinaemia occurs secondary to insulin resistance and is associated with increased risk of cardiovascular disease and diabetes mellitus. Insulin-sensitising agents such as metformin may be effective in treating PCOS-related anovulation. OBJECTIVES: To evaluate the effectiveness and safety of insulin-sensitising drugs in improving reproductive and metabolic outcomes for women with PCOS undergoing ovulation induction...
November 29, 2017: Cochrane Database of Systematic Reviews
Nicola-Xan Hutchinson, Allen Gibbs, Amanda Tonks, Benjamin D Hope-Gill
Dry cough is a common symptom described in patients with Idiopathic Pulmonary Fibrosis (IPF) and impairs quality of life. The exact mechanisms causing cough in IPF remain unclear, however evidence suggests altered cough neurophysiology and sensitisation plays a role; IPF patients have an enhanced cough reflex sensitivity to inhaled capsaicin. The Transient Receptor Potential Vanniloid-1 channel (TRPV-1) has a role in the cough reflex and airway expression is increased in patients with chronic cough. The Ankyrin-1 receptor (TRPA-1) is often co-expressed...
2017: PloS One
L Arendt-Nielsen, B Morlion, S Perrot, A Dahan, A Dickenson, H G Kress, C Wells, D Bouhassira, A Mohr Drewes
Different neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features...
February 2018: European Journal of Pain: EJP
Darren Beales, Robyn Fary, Cameron Little, Shruti Nambiar, Hakon Sveinall, Yen Leng Yee, Brigitte Tampin, Tim Mitchell
Hereditary neuropathy with liability to pressure palsy (HNPP) has historically been considered a pain-free condition, though some people with HNPP also complain of pain. This study characterised persistent pain in people with HNPP. Participants provided cross-sectional demographic data, information on the presence of neurological and persistent pain symptoms, and the degree to which these interfered with daily life. The painDETECT and Central Sensitization Inventory questionnaires were used to indicate potential neuropathic, central sensitisation and musculoskeletal (nociceptive) pain mechanisms...
December 2017: Journal of Neurology
Susan R Sama, David Kriebel, Rebecca J Gore, Rebecca DeVries, Richard Rosiello
INTRODUCTION: This study investigated the hypothesis that common environmental chemical exposures with known irritant or sensitising properties trigger exacerbations for patients with chronic obstructive pulmonary disease (COPD). METHODS: We conducted a case cross-over study in 168 patients with COPD who were members of a disease management group in central Massachusetts. Participants completed a baseline health survey and several short exposure surveys. Exposure surveys were administered by a nurse when a participant telephoned to report an exacerbation (case periods) and at a maximum of three randomly identified control periods when they were not experiencing an exacerbation...
2017: BMJ Open Respiratory Research
Jared M Campbell, Natalia Adanichkin, Rochelle Kurmis, Zachary Munn
This systematic review investigated the effectiveness and safety of intensive insulin therapy (IIT), insulin secretagogues and sensitisers in burn patients. PubMed, Embase, and Cochrane central were searched from 1990 to 2016. Title/abstract screening, full-text review, critical appraisal and data extraction were carried out by two independent reviewers. Inclusion criteria were hospitalised burn patients, IIT, insulin sensitisers or secretagogues and the outcomes mortality, length of stay, resting energy expenditure, blood glucose, catabolism, or complications...
October 10, 2017: Burns: Journal of the International Society for Burn Injuries
Sarah A Woller, Kelly A Eddinger, Maripat Corr, Tony L Yaksh
The nervous system detects and interprets a variety of chemical, mechanical, and thermal stimuli. In the face of tissue injury, local inflammatory products perpetuate ongoing activity and sensitisation of the peripheral nerve termini. This ongoing activity evokes a state of robust spinal facilitation mediated by a number of local circuits, the net effect yielding an enhanced message of nociception to higher centres. This messaging typically wanes with the resolution of inflammation or wound healing. However, there are situations in which peripheral and central components of the pain transmission pathway extend and enhance the pain state, leading to a persistent hypersensitivity, e...
September 2017: Clinical and Experimental Rheumatology
Delfien Syx, Inge De Wandele, Lies Rombaut, Fransiska Malfait
Chronic widespread pain is a common complaint among individuals affected by generalised joint hypermobility. In the absence of other conditions that cause chronic pain, these individuals are usually diagnosed with joint hypermobility syndrome (JHS). JHS is a multifactorial trait with a strong genetic basis, but no specific genetic markers. Clinical overlap of JHS is seen with heritable connective tissue disorders, particularly with the Ehlers-Danlos syndrome, hypermobile type (hEDS). The Ehlers-Danlos syndromes (EDS) comprise a heterogeneous group of rare monogenic conditions that are characterised by joint hypermobility, skin and vascular fragility and generalised connective tissue friability, and are caused by genetic defects in an array of extracellular matrix genes...
September 2017: Clinical and Experimental Rheumatology
Jo Nijs, Jacqui Clark, Anneleen Malfliet, Kelly Ickmans, Lennard Voogt, Sanneke Don, Hester den Bandt, Dorien Goubert, Jeroen Kregel, Iris Coppieters, Wim Dankaerts
Conservative, surgical and pharmacological strategies for chronic low back pain (CLBP) management offer at best modest effect sizes in reducing pain and related disability, indicating a need for improvement. Such improvement may be derived from applying contemporary pain neuroscience to the management of CLBP. Current interventions for people with CLBP are often based entirely on a "biomedical" or "psychological" model without consideration of information concerning underlying pain mechanisms and contemporary pain neuroscience...
September 2017: Clinical and Experimental Rheumatology
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