Central nervous system mast cells in peripheral inflammatory nociception

<p>Abstract</p> <p>Background</p> <p>Functional aspects of mast cell-neuronal interactions remain poorly understood. Mast cell activation and degranulation can result in the release of powerful pro-inflammatory mediators such as histamine and cytokines. Cerebral dural mast cells have been proposed to modulate meningeal nociceptor activity and be involved in migraine pathophysiology. Little is known about the functional role of spinal cord dural mast cells. In this study, we examine their potential involvement in nociception and synaptic plasticity in superficial spinal dorsal horn. Changes of lower spinal cord dura mast cells and their contribution to hyperalgesia are examined in animal models of peripheral neurogenic and non-neurogenic inflammation.</p> <p>Results</p> <p>Spinal application of supernatant from activated cultured mast cells induces significant mechanical hyperalgesia and long-term potentiation (LTP) at spinal synapses of C-fibers. Lumbar, thoracic and thalamic preparations are then examined for mast cell number and degranulation status after intraplantar capsaicin and carrageenan. Intradermal capsaicin induces a significant percent increase of lumbar dural mast cells at 3 hours post-administration. Peripheral carrageenan in female rats significantly increases mast cell density in the lumbar dura, but not in thoracic dura or thalamus. Intrathecal administration of the mast cell stabilizer sodium cromoglycate or the spleen tyrosine kinase (Syk) inhibitor BAY-613606 reduce the increased percent degranulation and degranulated cell density of lumbar dural mast cells after capsaicin and carrageenan respectively, without affecting hyperalgesia.</p> <p>Conclusion</p> <p>The results suggest that lumbar dural mast cells may be sufficient but are not necessary for capsaicin or carrageenan-induced hyperalgesia.</p

Posterior Beta and Anterior Gamma Oscillations Predict Cognitive Insight

Pioneering neuroimaging studies on insight have revealed neural correlates of the emotional “Aha!” component of the insight process, but neural substrates of the cognitive component, such as problem restructuring (a key to transformative reasoning), remain a mystery. Here, multivariate electroencephalogram signals were recorded from human participants while they solved verbal puzzles that could create a small-scale experience of cognitive insight. Individuals responded as soon as they reached a solution and provided a rating of subjective insight. For unsolved puzzles, hints were provided after 60 to 90 sec. Spatio-temporal signatures of brain oscillations were analyzed using Morlet wavelet transform followed by exploratory parallel-factor analysis. A consistent reduction in beta power (15–25 Hz) was found over the parieto-occipital and centro-temporal electrode regions on all four conditions—(a) correct (vs. incorrect) solutions, (b) solutions without (vs. with) external hint, (c) successful (vs. unsuccessful) utilization of the external hint, and d) self-reported high (vs. low) insight. Gamma band (30–70 Hz) power was increased in right fronto-central and frontal electrode regions for conditions (a) and (c). The effects occurred several (up to 8) seconds before the behavioral response. Our findings indicate that insight is represented by distinct spectral, spatial, and temporal patterns of neural activity related to presolution cognitive processes that are intrinsic to the problem itself but not exclusively to one's subjective assessment of insight

The design and protocol of acupuncture for migraine prophylaxis: A multicenter randomized controlled trial

Background: Many studies have already reported encouraging results in the prophylactic therapy of migraine by acupuncture, but there seems to be a lack of high quality randomized controlled trials from China. We design and perform a randomized controlled clinical trial to evaluate the efficacy of acupuncture compared with flunarizine in the prophylactic therapy of patients with migraine without aura in China. Methods: This trial is a multicenter, prospective, randomized controlled clinical trial. The 140 migraine patients are randomly allocated to two different groups. The acupuncture groups (n = 70) is treated with acupuncture and placebo medicine; while the control group (n = 70) is treated with sham acupuncture and medicine (Flunarizine). Both Flunarizine and placebo are taken 10 mg once per night for the first 2 weeks and then 5 mg once per night for the next 2 weeks. Patients in both groups receive 12 sessions of verum/sham acupuncture in 4 weeks. Discussion: The study design and the long term clinical practice of acupuncturists guarantee a high external validity for the results. The results of our trial will be helpful to supply the evidence on the efficacy of acupuncture for migraine prophylaxis in China. Trial Registration: The trial is registered at Controlled Clinical Trials: ISRCTN49839714.Medicine, Research &amp; ExperimentalSCI(E)0ARTICLEnull1

Deconstructing Insight: EEG Correlates of Insightful Problem Solving

Background: Cognitive insight phenomenon lies at the core of numerous discoveries. Behavioral research indicates four salient features of insightful problem solving: (i) mental impasse, followed by (ii) restructuring of the problem representation, which leads to (iii) a deeper understanding of the problem, and finally culminates in (iv) an “Aha!” feeling of suddenness and obviousness of the solution. However, until now no efforts have been made to investigate the neural mechanisms of these constituent features of insight in a unified framework. Methodology/Principal Findings: In an electroencephalographic study using verbal remote associate problems, we identified neural correlates of these four features of insightful problem solving. Hints were provided for unsolved problems or after mental impasse. Subjective ratings of the restructuring process and the feeling of suddenness were obtained on trial-by-trial basis. A negative correlation was found between these two ratings indicating that sudden insightful solutions, where restructuring is a key feature, involve automatic, subconscious recombination of information. Electroencephalogram signals were analyzed in the space×time×frequency domain with a nonparametric cluster randomization test. First, we found strong gamma band responses at parieto-occipital regions which we interpreted as (i) an adjustment of selective attention (leading to a mental impasse or to a correct solution depending on the gamma band power level) and (ii) encoding and retrieval processes for the emergence of spontaneous new solutions. Secondly, we observed an increased upper alpha band response in right temporal regions (suggesting active suppression of weakly activated solution relevant information) for initially unsuccessful trials that after hint presentation led to a correct solution. Finally, for trials with high restructuring, decreased alpha power (suggesting greater cortical excitation) was observed in right prefrontal area. Conclusions/Significance: Our results provide a first account of cognitive insight by dissociating its constituent components and potential neural correlates