Structure of laponite-styrene precursor dispersions for production of advanced polymer-clay nanocomposites

One method for production of polymer-clay nanocomposites involves dispersal of surface-modified clay in a polymerisable monomeric solvent, followed by fast in situ polymerisation. In order to tailor the properties of the final material we aim to control the dispersion state of the clay in the precursor solvent. Here, we study dispersions of surface-modified Laponite, a synthetic clay, in styrene via large-scale Monte-Carlo simulations and experimentally, using small angle X-ray and static light scattering. By tuning the effective interaction between simulated laponite particles we are able to reproduce the experimental scattering intensity patterns for this system, with good accuracy over a wide range of length scales. However, this agreement could only be obtained by introducing a permanent electrostatic dipole moment into the plane of each Laponite particle, which we explain in terms of the distribution of substituted metal atoms within each Laponite particle. This suggests that Laponite dispersions, and perhaps other clay suspensions, should display some of the structural characteristics of dipolar fluids. Our simulated structures show aggregation regimes ranging from networks of long chains to dense clusters of Laponite particles, and we also obtain some intriguing ‘globular’ clusters, similar to capsids. We see no indication of any ‘house-of-cards’ structures. The simulation that most closely matches experimental results indicates that gel-like networks are obtained in Laponite dispersions, which however appear optically clear and non-sedimenting over extended periods of time. This suggests it could be difficult to obtain truly isotropic equilibrium dispersion as a starting point for synthesis of advanced polymer-clay nanocomposites with controlled structures

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Sensitization and Interoception as Key Neurological Concepts in Osteopathy and Other Manual Medicines

Historically, approaches used in manual medicine to explain patient reported symptoms have been focused on the so-called exteroceptive paradigm. Arguably, this mindset lacks an appropriate "reading system" able to interpret musculoskeletal disorders from a different perspective, where the properties of the nervous system are embraced into a more holistic and functional-related context. Interestingly, if the underpinning mechanisms of a given treatment scenario/effect are taking into account, the majority of research outcomes focuses on a proprioceptive/exteroceptive explanation, leaving ting aside the additional or even central role of interoception. Currently, to date, the application of theoretical knowledge acquired on the relatively recent neuroscientific concepts and evidence concerning of interoception, sensitization, touch, autonomic functions, inflammation, and pain into a clinical/research manual medicine scenario is lacking, even if theoretically, the impact on the possible etiological mechanisms and treatment effects seems to be important. Here, we propose the conceptual foundations for a new way of interpreting and reading patients' clinical reported outcomes scenario based on interoception and sensitization. We argue that this will provide a foundation to create the ground for future research focusing on the hypotheses that manual therapies, specifically osteopathy, can intercede with sensitization states, at all levels, using interoceptive pathways

Involvement of EphB1 Receptors Signalling in Models of Inflammatory and Neuropathic Pain

EphB receptors tyrosine kinases and ephrinB ligands were first identified as guidance molecules involved in the establishment of topographical mapping and connectivity in the nervous system during development. Later in development and into adulthood their primary role would switch from guidance to activity-dependent modulation of synaptic efficacy. In sensory systems, they play a role in both the onset of inflammatory and neuropathic pain, and in the establishment of central sensitisation, an NMDA-mediated form of synaptic plasticity thought to underlie most forms of chronic pain. We studied wild type and EphB1 knockout mice in a range of inflammatory and neuropathic pain models to determine 1), whether EphB1 expression is necessary for the onset and/or maintenance of persistent pain, regardless of origin; 2), whether in these models cellular and molecular changes, e.g. phosphorylation of the NR2B subunit of the NMDA receptor, increased c-fos expression or microglial activation, associated with the onset of pain, are affected by the lack of functional EphB1 receptors. Differences in phenotype were examined behaviourally, anatomically, biochemically and electrophysiologically. Our results establish firstly, that functional EphB1 receptors are not essential for the development of normal nociception, thermal or mechanical sensitivity. Secondly, they demonstrate a widespread involvement of EphB1 receptors in chronic pain. NR2B phosphorylation, c-fos expression and microglial activation are all reduced in EphB1 knockout mice. This last finding is intriguing, since microglial activation is supposedly triggered directly by primary afferents, therefore it was not expected to be affected. Interestingly, in some models of long-term pain (days), mechanical and thermal hyperalgesia develop both in wild type and EphB1 knockout mice, but recovery is faster in the latter, indicating that in particular models these receptors are required for the maintenance, rather than the onset of, thermal and mechanical hypersensitivity. This potentially makes them an attractive target for analgesic strategies

Presynaptically Localized Cyclic GMP-Dependent Protein Kinase 1 Is a Key Determinant of Spinal Synaptic Potentiation and Pain Hypersensitivity

Electrophysiological and behavioral experiments in mice reveal that a cGMP-dependent kinase amplifies neurotransmitter release from peripheral pain sensors, potentiates spinal synapses, and leads to exaggerated pain

Applications of sensory and physiological measurement in oral‐facial dental pain

Dentists regularly employ a variety of self‐report and sensory techniques to aid in the diagnosis and treatment of tooth‐related disease. Many of these techniques leverage principles borrowed from psychophysics, the quantitative measurement of the relationship between stimuli and evoked sensations, which falls under the larger umbrella of quantitative sensory testing (QST). However, most clinicians fail to meet the bar for what could be considered quantitative sensory testing, and instead focus on qualitative and dichotomous “yes/no” aspects of sensory experience. With our current subjective measurements for pain assessments, diagnosis and treatment of dental pain in young children and individuals (any age) with severe cognitive impairment rely extensively on third‐party observations. Consequently, the limitation of inadequate pain diagnosis can lead to poor pain management. In this review, it discusses mechanisms that underlie acute and chronic dental pain. It details the measurement of somatosensory responses and pulpal blood flow as objective measures of tooth health and pain. It proposes that bridging these varied methodologies will significantly improve diagnosis and treatment of orofacial pain and pathology. It concludes that improving the precision of sensory measurements could yield important improvements in diagnostic challenges in pulpal pathology for noncommunicative and cognitively impaired individuals.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146659/1/scd12323.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146659/2/scd12323_am.pd

Bilateral Sensory Abnormalities in Patients with Unilateral Neuropathic Pain; A Quantitative Sensory Testing (QST) Study

In patients who experience unilateral chronic pain, abnormal sensory perception at the non-painful side has been reported. Contralateral sensory changes in these patients have been given little attention, possibly because they are regarded as clinically irrelevant. Still, bilateral sensory changes in these patients could become clinically relevant if they challenge the correct identification of their sensory dysfunction in terms of hyperalgesia and allodynia. Therefore, we have used the standardized quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain (DFNS) to investigate somatosensory function at the painful side and the corresponding non-painful side in unilateral neuropathic pain patients using gender- and age-matched healthy volunteers as a reference cohort. Sensory abnormalities were observed across all QST parameters at the painful side, but also, to a lesser extent, at the contralateral, non-painful side. Similar relative distributions regarding sensory loss/gain for non-nociceptive and nociceptive stimuli were found for both sides. Once a sensory abnormality for a QST parameter at the affected side was observed, the prevalence of an abnormality for the same parameter at the non-affected side was as high as 57% (for Pressure Pain Threshold). Our results show that bilateral sensory dysfunction in patients with unilateral neuropathic pain is more rule than exception. Therefore, this phenomenon should be taken into account for appropriate diagnostic evaluation in clinical practice. This is particularly true for mechanical stimuli where the 95% Confidence Interval for the prevalence of sensory abnormalities at the non-painful side ranges between 33% and 50%