Posterior-superior insula repetitive transcranial magnetic stimulation reduces experimental tonic pain and pain-related cortical inhibition in humans.

High frequency repetitive transcranial magnetic stimulation (rTMS) to the posterior-superior insula (PSI) may produce analgesic effects. However, the alterations in cortical activity during PSI-rTMS analgesia remain poorly understood. The present study aimed to determine whether tonic capsaicin-induced pain and cortical inhibition (indexed using TMS-electroencephalography) are modulated by PSI-rTMS.

Facilitation of Early and Middle Latency SEP after tDCS of M1: No Evidence of Primary Somatosensory Homeostatic Plasticity.

Homeostatic plasticity is a mechanism that stabilizes cortical excitability within a physiological range. Most homeostatic plasticity protocols have primed and tested the homeostatic response of the primary motor cortex (M1). This study investigated if a homeostatic response could be recorded from the primary sensory cortex (S1) after inducing homeostatic plasticity in M1.

Effects of pain on cortical homeostatic plasticity in humans: a systematic review.

Homeostatic plasticity (HP) is a negative feedback mechanism that prevents excessive facilitation or depression of cortical excitability (CE). Cortical HP responses in humans have been investigated by using 2 blocks of noninvasive brain stimulation with a no-stimulation block in between. A healthy HP response is characterized by reduced CE after 2 excitatory stimulation blocks and increased CE when using inhibitory stimulation.

Quantitative determination of the binding capabilities of individual large-ring cyclodextrins in complex mixtures.

Large-ring cyclodextrins (CDs) are a comparatively unexplored family of macrocycles. We use high-resolution H-C HSQC NMR experiments to resolve the anomeric signals of at least 13 different size CDs in a mixture. Using a single titration experiment, we can quantify the individual binding capabilites of these structurally-related hosts, avoiding the need for cumbersome isolation.

Light-controlled enzymatic synthesis of γ-CD using a recyclable azobenzene template.

Cyclodextrins (CDs) are important molecular hosts for hydrophobic guests in water and extensively employed in the pharmaceutical, food and cosmetic industries to encapsulate drugs, flavours and aromas. Compared with α- and β-CD, the wide-scale use of γ-CD is currently limited due to costly production processes. We show how the yield of γ-CD in the enzymatic synthesis of CDs can be increased 5-fold by adding a tetra--isopropoxy-substituted azobenzene template irradiated at 625 nm (to obtain the -()-isomer) to direct the synthesis.

Effects of Novel Vibro-Acupuncture on Healthy Subjects and Those with Experimental and Clinical Pain as Assessed by Quantitative Sensory Testing.

Background: To investigate the analgesic effects of vibro-acupuncture (VA), a novel acuvibrator was developed. Objectives: To compare the analgesic effects of VA with those of manual acupuncture (MA) and placebo acupuncture (PA) on subjects with normal sensory perception (Study I), experimentally induced acute pain (Study II), and clinical chronic pain (Study III).

Methods: Thirty healthy volunteers (21 males, age: 20-30 years) participated in Study I.

pH-Responsive templates modulate the dynamic enzymatic synthesis of cyclodextrins.

Product selection in the dynamic enzymatic synthesis of cyclodextrins can be controlled by changing the pH. Using cyclodextrin glucanotransferase to make labile the glycosidic linkages in cyclodextrins (CDs), we generate a dynamic combinatorial library of interconverting linear and cyclic α-1,4-glucans. Templates can be employed to favour the selective production of specific CDs and, herein, we show that by using ionisable templates, the synthesis of α-CD or β-CD can be favoured by simply changing the pH.

Unnatural cyclodextrins can be accessed from enzyme-mediated dynamic combinatorial libraries.

Dynamic systems of cyclodextrins (CDs) enabled by a native cyclodextrin glucanotransferase (CGTase) can incorporate unnatural glucopyranose-derived building blocks, expanding the applicability of enzyme-mediated dynamic combinatorial chemistry by using synthetically modified substrates. Starting dynamic combinatorial libraries from CDs with a single 6-modified glucopyranose results in a dynamic mixture of CDs containing several modified glucopyranoses. The relative concentrations of modified α, β or γ-CDs can be controlled by the addition of templates, providing a novel way to access modified CDs.

Modulation of offset analgesia in patients with chronic pain and healthy subjects - a systematic review and meta-analysis.

Objectives: Offset analgesia (OA) induces a brief pain inhibition and studies suggest OA impairment in patients with chronic pain when compared to healthy subjects. Conditioned pain modulation remains the most studied descending pain inhibitory control mechanism and is modulated by centrally-acting analgesics. Since OA may be mediated by similar neural substrates as conditioned pain modulation, understanding if OA is a peripheral or central proxy of pain modulation is important.

Chaotropic and Kosmotropic Anions Regulate the Outcome of Enzyme-Mediated Dynamic Combinatorial Libraries of Cyclodextrins in Two Different Ways.

We demonstrate how different anions from across the Hofmeister series can influence the behavior of enzyme-mediated dynamic combinatorial libraries of cyclodextrins (CDs). Using cyclodextrin glucanotransferase to catalyze reversible transglycosylation, dynamic mixtures of interconverting cyclodextrins can be formed wherein the relative concentrations of α-CD, β-CD and γ-CD is determined by their intrinsic stabilities and any stabilizing influences of added template (guest) molecules. Here, we find that addition of high concentrations of kosmotropic anions can be used to enhance the effects of added hydrophobic templates, while chaotropic anions can themselves act as templates, causing predictable and significant changes in the cyclodextrin composition due to weak, but specific, binding interactions with α-CD.

Protocols for inducing homeostatic plasticity reflected in the corticospinal excitability in healthy human participants: A systematic review and meta-analysis.

Homeostatic plasticity complements synaptic plasticity by stabilising neural activity within a physiological range. In humans, homeostatic plasticity is investigated using two blocks of non-invasive brain stimulation (NIBS) with an interval without stimulation between blocks. The aim of this systematic review and meta-analysis was to investigate the effect of homeostatic plasticity induction protocols on motor evoked potentials (MEP) in healthy participants.

The Modulatory Effect of Quantitative Sensory Testing in Shoulder Pain: A Systematic Review and Meta-Analysis.

Background: The underlying mechanisms for shoulder pain (SP) are still widely unknown. Previous reviews have reported signs of altered pain processing in SP measured with quantitative sensory testing (QST). Evidence suggests that QST might hold predictive value for SP after an intervention, yet it is not known whether QST profiles can be modulated in response to different treatments.

Building up cyclodextrins from scratch - templated enzymatic synthesis of cyclodextrins directly from maltose.

Cyclodextrins (CDs) are commercially produced via enzymatic breakdown of starch or amylose. In contrast, we show that cyclodextrins can be synthesised directly from the disaccharide maltose in good yields by exploiting the use of templates to favour the enzymatic build-up of cyclodextrins. Using cyclodextrin glucanotransferase to catalyse reversible transglycosylation, and 1-adamantane carboxylic acid as the template, we can synthesise β-CD from maltose in approximately 70% yield.

The Combination of Preoperative Pain, Conditioned Pain Modulation, and Pain Catastrophizing Predicts Postoperative Pain 12 Months After Total Knee Arthroplasty.

Objectives: Approximately 20% of knee osteoarthritis patients undergoing total knee arthroplasty (TKA) report chronic postoperative pain. Studies suggest that preoperative variables such as impaired descending pain control, catastrophizing, function, and neuropathic pain-like symptoms may predict postoperative pain 12 months after TKA, but the combined prediction value of these factors has not been tested. The current prospective cohort study aimed to combine preoperative risk factors to investigate the predictive value for postoperative pain 12 months after TKA.

The predictive value of quantitative sensory testing: a systematic review on chronic postoperative pain and the analgesic effect of pharmacological therapies in patients with chronic pain.

Studies have suggested that quantitative sensory testing (QST) might hold a predictive value for the development of chronic postoperative pain and the response to pharmacological interventions. This review systematically summarizes the current evidence on the predictive value of QST for chronic postoperative pain and the effect of pharmacological interventions. The main outcome measures were posttreatment pain intensity, pain relief, presence of moderate-to-severe postoperative pain, responders of 30% and 50% pain relief, or validated questionnaires on pain and disability.

Tuning the Outcome of Enzyme-Mediated Dynamic Cyclodextrin Libraries to Enhance Template Effects.

Enzyme-mediated dynamic combinatorial chemistry combines the concept of thermodynamically controlled covalent self-assembly with the inherent biological relevance of enzymatic transformations. A system of interconverting cyclodextrins has been explored, in which the glycosidic linkage is rendered dynamic by the action of cyclodextrin glucanotransferase (CGTase). External factors, such as pH, temperature, solvent, and salinity are reported to modulate the composition of the dynamic cyclodextrin library.

Enzyme-mediated dynamic combinatorial chemistry allows out-of-equilibrium template-directed synthesis of macrocyclic oligosaccharides.

We show that the outcome of enzymatic reactions can be manipulated and controlled by using artificial template molecules to direct the self-assembly of specific products in an enzyme-mediated dynamic system. Specifically, we utilize a glycosyltransferase to generate a complex dynamic mixture of interconverting linear and macrocyclic α-1,4-d-glucans (cyclodextrins). We find that the native cyclodextrins (α, β and γ) are formed out-of-equilibrium as part of a kinetically trapped subsystem, that surprisingly operates transiently like a Dynamic Combinatorial Library (DCL) under thermodynamic control.

Total sleep deprivation increases pain sensitivity, impairs conditioned pain modulation and facilitates temporal summation of pain in healthy participants.

Chronic pain patients often suffer from insomnia or impaired sleep which has been associated with increased pain sensitivity, but a limited amount of studies have investigated the effects of total sleep deprivation on central pain mechanisms. Therefore, the aim of this study was to determine the effects of total sleep deprivation on temporal summation, conditioned pain modulation, thermal and pressure pain sensitivity in healthy participants. Twenty-four healthy participants took part in this two-session trial.

Light-controlled out-of-equilibrium assembly of cyclodextrins in an enzyme-mediated dynamic system.

We show that the selective enzymatic synthesis of specific cyclodextrins can be modulated using light. We use enzyme-mediated dynamic combinatorial chemistry to generate a mixture of interconverting linear and cyclic α-1,4-glucans, and employ an azobenzene photoswitch as a template. Using UV or blue light to switch between photostationary states with different azobenzene cis/trans isomeric ratios, we can promote the out-of-equilibrium assembly of either α-cyclodextrin or β-cyclodextrin.

Practical Use of the Navigate Pain Application for the Assessment of the Area, Location, and Frequency of the Pain Location in Young Soccer Goalkeepers.

Next to winning, minimizing injuries during training and matches is one of the primary goals of professional team sports games. Soreness and pain can be early indicators and risk factors for acute or long-term injuries. Monitoring pain intensity and duration, as well as potential sources, are useful for planning practices and can be effective means for preventing injury.

Corticomotor excitability reduction induced by experimental pain remains unaffected by performing a working memory task as compared to staying at rest.

Experimental pain inhibits primary motor cortex (M1) excitability. Attenuating pain-related inhibition of M1 excitability may be useful during rehabilitation in individuals with pain. One strategy to attenuate M1 excitability is to influence prefrontal and premotor cortex activity.

Pain-Induced Reduction in Corticomotor Excitability Is Counteracted by Combined Action-Observation and Motor Imagery.

Musculoskeletal pain reduces corticomotor excitability (CE) and methods modulating such CE reduction remain elusive. This study aimed to modulate pain-induced CE reduction by performing action observation and motor imagery (AOMI) during experimental muscle pain. Twelve healthy participants participated in 3 cross-over and randomized sessions separated by 1 week.

Exceptionally rapid oxime and hydrazone formation promoted by catalytic amine buffers with low toxicity.

Hydrazone and oxime bond formation between α-nucleophiles ( hydrazines, alkoxy-amines) and carbonyl compounds (aldehydes and ketones) is convenient and is widely applied in multiple fields of research. While the reactants are simple, a substantial drawback is the relatively slow reaction at neutral pH. Here we describe a novel molecular strategy for accelerating these reactions, using bifunctional buffer compounds that not only control pH but also catalyze the reaction.