Civil Discovery of Documents Held by a Grand Jury

Brief overview of used methods and the association between pain and CGRP in each category. (DOC 72 kb

Additional file 1: of Cilostazol induced migraine does not respond to sumatriptan in a double blind trial

Datasheet Cilostazol MO. (XLSX 25 kb

Contrast analysis results for painful heat functional MRI activation at baseline (before infusion of CGRP).

<p>NOTE: Two ROIs usually active in pain (anterior cingulate cortex and anterior insula) are not identified due to the distortion of the images.</p

Contrast analysis results for painful heat functional MRI activation after sumatriptan administration on the CGRP day.

<p>Contrast analysis results for painful heat functional MRI activation after sumatriptan administration on the CGRP day.</p

BOLD-signal during CGRP infusion: Group BOLD-fMRI results for noxious heat simulations to the V1 area on the CGRP day; differences between neuronal activation at T₄₀ (after CGRP infusion) and T_-5 (baseline).

<p>The activated regions-of-interest are shown in three projections. CGRP infusion resulted in positive activation in insula and bilateral activation in the brainstem, while negative activation was recorded in the caudate nuclei, thalamus and cingulate cortex.</p

Study Setup: Reconstruction of the study setup.

<p>The subjects would be placed in the supine position inside the MRI scanner. The upper boarder of the eyebrows was used to centralize the subjects position in the scanner. The thermode was fitted in between the bars of the coil and then attached to the V1 area of the forehead. A custom build MRI compatible carrying arm and adhesive tape was used to ensure that only the heating element of the thermode came in contact with the skin. The subjects would be wearing ear protection under the whole duration of the MRI scans.</p

Pain score: Boxplot of pain scores (NRS) after noxious heat stimulation at baseline, before sumatriptan and after sumatriptan administration.

<p>A (left side) show the pain scores on the CGRP days. B (Right side) show the pain scores on the placebo day. There was no difference in pain score between the two experimental days at baseline (<i>P = 1</i>.<i>0</i>), before sumatriptan (<i>P = 0</i>.<i>87</i>) and after sumatriptan (<i>P = 0</i>.<i>36</i>) administration.</p

Headache score: Boxplot of median headache on the CGRP day before (T₄₀) and after sumatriptan injection (T₆₅).

<p>Stars (*) symbolize outliers. Before sumatriptan administration there was a median headache of 1.5 on the verbal rating scale (VRS) (range: 0–4). After treatment with sumatriptan the median headache intensity dropped to VRS 1.0 (range 0–3) <i>(P = 0</i>.<i>099)</i>.</p

BOLD-signal after sumatriptan administration: Group BOLD-fMRI results for noxious heat simulations to the V1 area on the CGRP day; differences between neuronal activation at T₆₀ (after sumatriptan) and T₄₀ (during CGRP infusion/before sumatriptan).

<p>The activated regions-of-interest are shown in three projections. Sumatriptan injection resulted in positive activation of the cingulate cortex.</p

Study design: All variables were recorded at fixed time points throughout the study.

<p>The anatomical image was recorded at T_-15. BOLD-fMRI scan after noxious heat stimulation with the thermode was recorded at T_-5 (baseline), at T₄₀ and T₆₀ (15 min after sumatriptan injection). Start of infusion was defined at T₀. According to the randomization code CGRP (1.5 μg/min) or placebo was infused over 20 min. Intervention with subcutaneous injection of sumatriptan was performed at T₄₅._.Hemodynamic variables, adverse event and headache intensity on the verbal rating scale (VRS) was recorded at 0, 5, 10, 15, 25, 35, 45, 55 and 65 min.</p