Anodal transcranial direct current stimulation over the primary motor cortex attenuates capsaicin‐induced dynamic mechanical allodynia and mechanical pain sensitivity in humans

BACKGROUND: Anodal transcranial direct current stimulation over the primary cortex has been shown to activate regions of the brain involved in the descending modulation of pain sensitivity. However, more research is required in order to dissect the spinal cord analgesic mechanisms associated with the development of central sensitisation. METHODS: In this randomised, double blind, cross over study 12 healthy participants had baseline mechanical stimulus response (S/R) functions measured before and after the development of capsaicin-induced ongoing pain sensitivity. The effects of 20 min of either real or sham transcranial direct current stimulation (tDCS, 2 mA) over the primary motor cortex on dynamic mechanical allodynia (DMA) and mechanical pain sensitivity (MPS) was then investigated. RESULTS: Topical application of capsaicin resulted in an increase in area under the pain ratings curve for both DMA (p < .01) and MPS (p < .01). The effects of tDCS on the area under the curve ratio (i.e. post/pre-treatment) revealed significant analgesic effects over DMA (p < .05) and MPS (p < .05) when compared to sham. CONCLUSIONS: This study demonstrates that anodal tDCS over the primary motor cortex can reduce both dynamic and static forms of mechanical pain sensitivity associated with the development of DMA and MPS, respectively. The use of tDCS may provide a novel mechanism-driven therapy in chronic pain patients with altered mechanical S/R functions

Mechanisms of Synapse formation and Maintenance: Insights From the Developing and Diseased Nervous System

ABSTRACT MECHANISMS OF SYNAPSE FORMATION AND MAINTENANCE: INSIGHTS FROM THE DEVELOPING AND DISEASED NERVOUS SYSTEM Ethan G. Hughes Rita J. Balice-Gordon, Ph.D. The formation and maintenance of synapses is essential for the central nervous system (CNS) to function. In the developing nervous system, the assembly of synaptic circuits is a complex and dynamic process, requiring the coordinated exchange of signals between pre- and postsynaptic neurons and surrounding glia. The maintenance and modulation of synaptic connections is required for normal CNS function and ongoing plasticity. The structural and functional integrity of synaptic connections is often modified or lost in the diseased nervous system, resulting in profound cognitive and behavioral deficits. While some aspects of the mechanisms underlying the formation, maintenance and plasticity of CNS synapses in the developing and diseased nervous system have been elucidated, many more remain to be understood. In my thesis work, I have examined the role of astrocytes in the development of GABAergic hippocampal synapses in in vitro models. I have also examined the maintenance of glutamatergic synapses in in vitro and in vivo models of anti-NMDAR encephalitis, an immune-mediated disorder of memory and behavior. First, I demonstrate that secreted factors released from astrocytes specifically increase GABAergic axon length, branching, and synaptogenesis, that these effects are not mediated by several well-known candidates, and that the secreted factors from astrocytes are proteins. Second, I examined the identity of the proteins released from astrocytes that affect GABAergic neurons using size fractionation, mass spectroscopy, and computational analyses. Third, I examined the cellular and synaptic mechanisms underlying anti-NMDAR encephalitis and investigated the effects of autoantibodies from patients with this disorder on the maintenance and function of CNS excitatory synapses. Together, my work extends our understanding of how neuron-glial communication modulates the formation of synapses in the developing brain, and how the disruption of synapse maintenance may underlie cognitive deficits in the diseased nervous system

The contribution of 211 particles to the mechanical reinforcement mechanism of 123 superconducting single domains

Hardness and fracture toughness of Dy-123 single-domains were studied by Vickers micro-indentation. A significant anisotropy of the mechanical properties was observed. Hardness tests give higher values when performed in (001) planes rather than in planes parallel to the c-axis. Moreover cracks pattern around the indentation follows preferential orientation in planes parallel to the c-axis whereas a classical ''four-cracks'' pattern is observed in the (001) planes. It has been possible to show the crucial role played by the 211-particles in the deviating mechanism of cracks and the relevance of the 211-particle distribution high homogeneity in the material.Comment: 14 pages, including 5 figures and 1 Table. submitted to Supercond. Sci. Techno

Frequency-dependent top-down modulation of temporal summation by anodal transcranial direct-current stimulation of the primary motor cortex in healthy adults

12 months embargo, now expired.Background Transcranial direct-current stimulation (tDCS) applied over the primary motor cortex has been shown to be effective in the treatment of a number of chronic pain conditions. However, there is a lack of understanding of the top-down analgesic mechanisms involved. Method In this study, we investigated the effects of tDCS on the facilitation of subjective sensory and pain scores using a transcutaneous electrically evoked measure of temporal summation. In this randomized, blinded, cross-over study healthy subjects received a single stimulus given at 0.9× pain threshold (pTh) over the L5 dermatome on the lateral aspect of the right leg, followed by a train of 5 stimuli given at 0.5, 1, 5 and 20 Hz before and after 20 min of sham or anodal tDCS (2 mA) applied over the primary motor cortex. Ratings of sensation and pain intensity were scored on a visual analogue scale (VAS). Results Temporal summation leading to pain only occurred at higher frequencies (5 and 20 Hz). Sham or real tDCS had no effect over temporal summation evoked at 5 Hz; however, there was a significant analgesic effect at 20 Hz. Sham or real tDCS had no effect over acute, single stimuli-evoked responses. Conclusion These results indicate that anodal tDCS applied to the primary motor cortex preferentially modulates temporal summation induced by high-frequency electrical stimulation-induced pain. The inhibitory effects of tDCS appear to be dynamic and dependent on the degree of spinal cord excitability and may explain the higher analgesic efficacy in patients with moderate to severe chronic pain symptoms. Significance The analgesic effects of tDCS are dependent on spinal cord excitability. This work provides insight into top-down modulation during acute pain and temporal summation. This knowledge may explain why tDCS has a higher analgesic efficacy in chronic pain patients

Evidence and modeling of turbulence bifurcation in L-mode confinement transitions on Alcator C-Mod

© 2020 Author(s). Analysis and modeling of rotation reversal hysteresis experiments show that a single turbulent bifurcation is responsible for the Linear to Saturated Ohmic Confinement (LOC/SOC) transition and concomitant intrinsic rotation reversal on Alcator C-Mod. Plasmas on either side of the reversal exhibit different toroidal rotation profiles and therefore different turbulence characteristics despite the profiles of density and temperature, which are indistinguishable within measurement uncertainty. Elements of this bifurcation are also shown to persist for auxiliary heated L-modes. The deactivation of subdominant (in the linear growth rate and contribution to heat transport) ion temperature gradient and trapped electron mode instabilities is identified as the only possible change in turbulence within a reduced quasilinear transport model across the reversal, which is consistent with the measured profiles and inferred heat and particle fluxes. Experimental constraints on a possible change from strong to weak turbulence, outside the description of the quasilinear model, are also discussed. These results indicate an explanation for the LOC/SOC transition that provides a mechanism for the hysteresis through the dynamics of subdominant modes and changes in their relative populations and does not involve a change in the most linearly unstable ion-scale drift-wave instability

Diffusion tensor imaging reveals changes in microstructural integrity along compressed nerve roots that correlate with chronic pain symptoms and motor deficiencies in elderly stenosis patients

Age-related degenerative changes in the lumbar spine frequently result in nerve root compression causing severe pain and disability. Given the increasing incidence of lumbar spinal disorders in the aging population and the discrepancies between the use of current diagnostic imaging tools and clinical symptoms, novel methods of nerve root assessment are needed. We investigated elderly patients with stenosis at L4-L5 or L5-S1 levels. Diffusion tensor imaging (DTI) was used to quantify microstructure in compressed L5 nerve roots and investigate relationships to clinical symptoms and motor neurophysiology. DTI metrics (i.e. FA, MD, AD and RD) were measured at proximal, mid and distal segments along compressed (i.e. L5) and intact (i.e. L4 or S1) nerve roots. FA was significantly reduced in compressed nerve roots and MD, AD and RD were significantly elevated in the most proximal segment of the nerve root studied. FA was significantly correlated with electrophysiological measures of root function: minimum F-wave latency and peripheral motor conduction time (PMCT). In addition, FA along the compressed root also correlated with leg pain and depression score. There was also a relationship between RD and anxiety, leg pain and disability score and AD correlated with depression score. Taken together, these data show that DTI metrics are sensitive to nerve root compression in patients with stenosis as a result of age-related lumbar degeneration. Critically, they show that the changes in microstructural integrity along compressed L5 nerve roots are closely related to a number of clinical symptoms associated with the development of chronic pain as well as neurophysiological assessments of motor function. These inherent relationships between nerve root damage and phenotype suggest that the use DTI is a promising method as a way to stratify treatment selection and predict outcomes

Collision number statistics for transport processes

Many physical observables can be represented as a particle spending some random time within a given domain. For a broad class of transport-dominated processes, we detail how it is possible to express the moments of the number of particle collisions in an arbitrary volume in terms of repeated convolutions of the ensemble equilibrium distribution. This approach is shown to generalize the celebrated Kac formula for the moments of residence times, which is recovered in the diffusion limit. Some practical applications are illustrated for bounded, unbounded and absorbing domains.Comment: 4 pages, 4 figure

Adverse effect of diabetes and hyperglycaemia on arterial stiffness in Europeans, South Asians, and African Caribbeans in the SABRE study

OBJECTIVES: Ethnic minority groups in the UK experience marked differences in cardiovascular disease risk. We investigated differences in arterial central haemodynamics, stiffness, and load in a tri-ethnic population-based cohort. METHODS: A total of 1312 participants (70 ± 6 years) underwent echocardiography and measurement of brachial and central blood pressure to assess central arterial haemodynamics including central pulse pressure (cPP), arterial stiffness [cPP/stroke volume (SV)], systemic vascular resistance (SVR), and load (Ea). RESULTS: Brachial and central SBPs were similar in all ethnic groups. Compared with Europeans, cPP, cPP/SV, and Ea were higher in South Asians. In contrast, cPP/SV was lower in African Caribbeans despite higher mean arterial pressure, higher SVR, and higher diabetes prevalence. cPP/SV and Ea remained significantly higher in South Asians and significantly lower in African Caribbeans after multivariate adjustment. Diabetes and higher HbA1c were more strongly associated with higher cPP/SV in South Asians than in Europeans (Pinteraction = 0.045 and 0.005, respectively); higher HbA1c was also more strongly associated with increased Ea in South Asians than Europeans (Pinteraction = 0.01). There was no evidence of an interaction between glycaemia and cPP/SV in African Caribbeans. CONCLUSIONS: Compared with Europeans, South Asians have unfavorable arterial function. Diabetes and hyperglycaemia have a more deleterious effect on cPP/SV and Ea in South Asians. In contrast, African Caribbeans have more favourable arterial function than Europeans and South Asians. These differences may contribute to the differential ethnic rates of cardiovascular disease

Novel coronary heart disease risk factors at 60-64 years and life course socioeconomic position: The 1946 British birth cohort.

Social disadvantage across the life course is associated with a greater risk of coronary heart disease (CHD) and with established CHD risk factors, but less is known about whether novel CHD risk factors show the same patterns. The Medical Research Council National Survey of Health and Development was used to investigate associations between occupational socioeconomic position during childhood, early adulthood and middle age and markers of inflammation (C-reactive protein, interleukin-6), endothelial function (E-selectin, tissue-plasminogen activator), adipocyte function (leptin, adiponectin) and pancreatic beta cell function (proinsulin) measured at 60-64 years. Life course models representing sensitive periods, accumulation of risk and social mobility were compared with a saturated model to ascertain the nature of the relationship between social class across the life course and each of these novel CHD risk factors. For interleukin-6 and leptin, low childhood socioeconomic position alone was associated with high risk factor levels at 60-64 years, while for C-reactive protein and proinsulin, cumulative effects of low socioeconomic position in both childhood and early adulthood were associated with higher (adverse) risk factor levels at 60-64 years. No associations were observed between socioeconomic position at any life period with either endothelial marker or adiponectin. Associations for C-reactive protein, interleukin-6, leptin and proinsulin were reduced considerably by adjustment for body mass index and, to a lesser extent, cigarette smoking. In conclusion, socioeconomic position in early life is an important determinant of several novel CHD risk factors. Body mass index may be an important mediator of these relationships

Diffusion tensor imaging of lumbar spinal nerves reveals changes in microstructural integrity following decompression surgery associated with improvements in clinical symptoms: A case report

The outcomes from spinal nerve decompression surgery are highly variable with a sizable proportion of elderly foraminal stenosis patients not regaining good pain relief. A better understanding of nerve root compression before and following decompression surgery and whether these changes are mirrored by improvements in symptoms may help to improve clinical decision-making processes. This case study used a combination of diffusion tensor imaging (DTI), clinical questionnaires and motor neurophysiology assessments before and up to 3 months following spinal decompression surgery. In this case report, a 70-year-old women with compression of the left L5 spinal nerve root in the L5-S1 exit foramina was recruited to the study. At 3 months following surgery, DTI revealed marked improvements in left L5 microstructural integrity to a similar level to that seen in the intact right L5 nerve root. This was accompanied by a gradual improvement in pain-related symptoms, mood and disability score by 3 months. Using this novel multimodal approach, it may be possible to track concurrent improvements in pain-related symptoms, function and microstructural integrity of compressed nerves in elderly foraminal stenosis patients undergoing decompression surgery