Approximation to pain-signaling network in humans by means of migraine.

Nociceptive signals are processed within a pain-related network of the brain. Migraine is a rather specific model to gain insight into this system. Brain networks may be described by white matter tracts interconnecting functionally defined gray matter regions. Here, we present an overview of the migraine-related pain network revealed by this strategy. Based on diffusion tensor imaging data from subjects in the Human Connectome Project (HCP) database, we used a global tractography approach to reconstruct white matter tracts connecting brain regions that are known to be involved in migraine-related pain signaling. This network includes an ascending nociceptive pathway, a descending modulatory pathway, a cortical processing system, and a connection between pain-processing and modulatory areas. The insular cortex emerged as the central interface of this network. Direct connections to visual and auditory cortical association fields suggest a potential neural basis of phono- or photophobia and aura phenomena. The intra-axonal volume (Vintra ) as a measure of fiber integrity based on diffusion microstructure was extracted using an innovative supervised machine learning approach in form of a Bayesian estimator. Self-reported pain levels of HCP subjects were positively correlated with tract integrity in subcortical tracts. No correlation with pain was found for the cortical processing systems.

Thyroid Diseases Are an Underestimated Risk Factor for Cerebral Venous Sinus Thrombosis.

Introduction: Cerebral venous sinus thrombosis (CVST) is a rare disease that generally accounts for just 1% of all strokes. Of the multiple risk factors that have been identified, the most common are genetic or acquired thrombophilia and the use of oral contraceptives, while the less common include local infections and mechanical causes. Thyroid diseases have been described as rare risk factors for CVST (<2% of all cases), without exact knowledge of the underlying pathophysiology. This retrospective study aimed to re-evaluate the relevance of thyroid disease as risk factor for CVST, with particular emphasis on hyperthyroidism. Patients and Methods: Confirmed cases of CVST were (re-)evaluated in terms of risk factors including thyroid parameters. Results were compared to previous data from the International Study on CVST. Results: Between 1996 and 2016, 182 patients with confirmed CVST were treated in our hospital with a median age of 44 years and a female proportion of 74.7%. Genetic or acquired thrombophilia along with the use of oral contraceptives were found to be the most common risk factors. Thyroid diseases were present in 20.9% of CVST patients; this included patients with previous (9.9%) and current thyroid dysfunction (11%). Discussion and Conclusions: Thyroid diseases may represent a more common risk factor for CVST than previously described. This holds true even if patients with current thyroid dysfunction are purely taken into account. However, 58% of patients had more than one additional risk factor, suggesting a multifactorial hypercoagulability. Clinical Trials Register: Registered at the German Clinical Trials Register: http://www.drks.de, DRKS00017044.

Release of CGRP from mouse brainstem slices indicates central inhibitory effect of triptans and kynurenate.

BACKGROUND: CGRP is contained in a substantial proportion of unmyelinated trigeminal neurons innervating intracranial tissues. Previously, we have described a hemisected rodent scull preparation and later the intact trigeminal ganglion to measure stimulated CGRP release from trigeminal afferents. METHODS: Here, we establish a preparation for examining CGRP release from central trigeminal terminals using single fresh slices of the mouse medullary brainstem. RESULTS: Basal and stimulated amount of CGRP substantially exceeded the detection level. Experiments were designed as matched pairs of at least six brainstem slices per animal. Stimulation with high potassium induced calcium-dependent and reversible CGRP release. Capsaicin stimulation of TRPV1 provoked concentration-dependent CGRP release. The anti-migraine drug naratriptan did not inhibit capsaicin-induced CGRP release from peripheral terminals but inhibited the release from brainstem slices. The glutamate antagonist kynurenate showed a similar pattern of site-specific inhibition of CGRP release. CONCLUSIONS: As observed earlier for other drugs used in the treatment of migraine this indicates that the central terminals in the spinal trigeminal nucleus may be the main site of action. The preparation allows evaluating the trigeminal brainstem as a pharmacological site of action.