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Shklover J.,Technion - Israel Institute of Technology | Weisman-Shomer P.,Technion - Israel Institute of Technology | Yafe A.,Technion - Israel Institute of Technology | Yafe A.,Pain Medicine Unit | Michael F.,Technion - Israel Institute of Technology
Nucleic Acids Research | Year: 2010

Gene promoters are enriched in guanine clusters that potentially fold into quadruplex structures. Such quadruplexes were implicated in the regulation of gene expression, plausibly by interacting with transcription factors. We showed previously that homodimers of the myogenic transcription factor MyoD bound in vitro most tightly bimolecular quadruplexes of promoter sequences of muscle-specific genes. By contrast, MyoD-E47 heterodimers formed tighter complexes with d(CANNTG) E-box motifs that govern muscle gene expression. Here, we show that DNA quadruplexes enhance in vivo MyoD and E-box-driven expression of a firefly luciferase (FL) reporter gene. HEK293 cells were transfected with FL expressing p4RTK-FL vector alone or together with MyoD expressing pEMSV-MyoD plasmid, with quadruplexes of α7 integrin or sarcomeric mitochondrial creatine kinase (sMtCK) muscle gene promoters or with a combination thereof. Whereas MyoD elevated by ̃10-fold the levels of FL mRNA and protein, the DNA quadruplexes by themselves did not affect FL expression. However, together with MyoD, quad-ruplex DNA increased by ̃35-fold the amounts of FL mRNA and protein. Without affecting its expression, DNA quadruplexes bound MyoD in the cells. Based on these results, we propose models for the regulation of muscle gene transcription by direct interaction of MyoD with promoter quadruplex structures. © The Author(s) 2010. Published by Oxford University Press. Source


Tampin B.,Curtin University Australia | Briffa N.K.,Curtin University Australia | Slater H.,Curtin University Australia | Slater H.,Pain Medicine Unit
European Journal of Pain (United Kingdom) | Year: 2013

Background: The painDETECT questionnaire (PD-Q) has been used as a tool to characterize sensory abnormalities in patients with persistent pain. This study investigated whether the self-reported sensory descriptors of patients with painful cervical radiculopathy (CxRAD) and patients with fibromyalgia (FM), as characterized by responses to verbal sensory descriptors from PD-Q (sensitivity to light touch, cold, heat, slight pressure, feeling of numbness in the main area of pain), were associated with the corresponding sensory parameters as demonstrated by quantitative sensory testing (QST). Methods: Twenty-three patients with CxRAD (eight women, 46.3 9.6 years) and 22 patients with FM (20 women, 46.1 ± 11.5 years) completed the PD-Q. Standardized QST of dynamic mechanical allodynia, cold and heat pain thresholds, pressure pain thresholds, mechanical and vibration detection thresholds, was recorded from the maximal pain area. Comparative QST data from 31 age-matched healthy controls (HCs; 15 women) were obtained. Results: Patients with CxRAD demonstrated a match between their selfreported descriptors and QST parameters for all sensory parameters except for sensitivity to light touch, and these matches were statistically significant compared with HC data (p 0.006). The FM group demonstrated discrepancies between the PD-Q and QST sensory phenotypes for all sensory descriptors, indicating that the self-reported sensory descriptors did not consistently match the QST parameters (p = ≤ 0.017). Conclusion: Clinicians and researchers should be cautious about relying on PD-Q as a stand-alone screening tool to determine sensory abnormalities in patients with FM. © 2012 European Federation of International Association. Source


Tampin B.,Curtin University Australia | Slater H.,Curtin University Australia | Slater H.,Pain Medicine Unit | Hall T.,Curtin University Australia | And 3 more authors.
Pain | Year: 2012

The aim of this study was to establish the somatosensory profiles of patients with cervical radiculopathy and patients with nonspecific neck-arm pain associated with heightened nerve mechanosensitivity (NSNAP). Sensory profiles were compared to healthy control (HC) subjects and a positive control group comprising patients with fibromyalgia (FM). Quantitative sensory testing (QST) of thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimulation was performed in the maximal pain area, the corresponding dermatome and foot of 23 patients with painful C6 or C7 cervical radiculopathy, 8 patients with NSNAP in a C6/7 dermatomal pain distribution, 31 HC and 22 patients with FM. For both neck-arm pain groups, all QST parameters were within the 95% confidence interval of HC data. Patients with cervical radiculopathy were characterised by localised loss of function (thermal, mechanical, vibration detection P <.009) in the maximal pain area and dermatome (thermal detection, vibration detection, pressure pain sensitivity P <.04), consistent with peripheral neuronal damage. Both neck-arm pain groups demonstrated increased cold sensitivity in their maximal pain area (P <.03) and the foot (P <.009), and this was also the dominant sensory characteristic in patients with NSNAP. Both neck-arm pain groups differed from patients with FM, the latter characterised by a widespread gain of function in most nociceptive parameters (thermal, pressure, mechanical pain sensitivity P <.027). Despite commonalities in pain characteristics between the 2 neck-arm pain groups, distinct sensory profiles were demonstrated for each group. © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. Source


Briggs A.M.,Government of Western Australia | Slater H.,Curtin University Australia | Slater H.,Pain Medicine Unit | Smith A.J.,Curtin University Australia | And 3 more authors.
European Journal of Pain (United Kingdom) | Year: 2013

Background: Evidence points to clinicians' beliefs and practice behaviours related to low back pain (LBP), which are discordant with contemporary evidence. While interventions to align beliefs and behaviours with evidence among clinicians have demonstrated effectiveness, a more sustainable and cost-effective approach to positively developing workforce capacity in this area may be to target the emerging workforce. The aim of this study was to investigate beliefs and clinical recommendations for LBP, and their alignment to evidence, in Australian university allied health and medical students. Methods: Final-year students in chiropractic, medicine, occupational therapy, pharmacy and physiotherapy disciplines in three Western Australian universities responded to a survey. Demographic data, LBP-related beliefs data [modified Health Care Providers Pain and Impact Relationship Scale (HC-PAIRS) and the Back Pain Beliefs Questionnaire (BBQ) ] and activity, rest and work clinical recommendations for an acute LBP clinical vignette were collected. Results: Six hundred two students completed the survey (response rate 74.6%). Cross-discipline differences in beliefs and clinical recommendations were observed (p > 0.001). Physiotherapy and chiropractic students reported significantly more helpful beliefs compared with the other disciplines, while pharmacy students reported the least helpful beliefs. A greater proportion of chiropractic and physiotherapy students reported guidelineconsistent recommendations compared with other disciplines. HC-PAIRS and BBQ scores were strongly associated with clinical recommendations, independent to the discipline of study and prior experience of LBP. Conclusions: Aligning cross-discipline university curricula with current evidence may provide an opportunity to facilitate translation of this evidence into practice with a focus on a consistent, cross-discipline approach to LBP management. © 2012 European Federation of International Association. Source


Lyon P.,University of South Australia | Cohen M.,St. Vincents Campus | Quintner J.,Pain Medicine Unit
Pain Medicine | Year: 2011

Objective. The study aimed to seek a unifying biological basis for the phenomena encompassed in fibromyalgia syndrome (chronic widespread pain and associated morbidities). Setting. While much progress has been made in the last decade in understanding chronic widespread pain, its pathogenesis remains stubbornly obscure and its treatment difficult. Two themes are gaining currency in the field: that chronic widespread pain is the result of central sensitization of nociception, and that chronic pain is somehow related to activation of a global stress response. Design. In this article we merge these two ideas within the perspective of evolutionary biology to generate a hypothesis about the critical molecular pathway involved in chronic stress response activation, namely substance P and its preferred receptor, neurokinin-1 (NK-1R), which has many empirically testable implications. Conclusion. Drawing on diverse findings in neurobiology, immunology, physiology, and comparative biology, we suggest that the form of central sensitization that leads to the profound phenomenological features of chronic widespread pain is part of a whole-organism stress response, which is evolutionarily conserved, following a general pattern found in the simplest living systems. Wiley Periodicals, Inc. Source

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