Objective:To determine whether erenumab, a new monoclonal antibody to the calcitonin gene-related peptide (CGRP) receptor, exerts functional central effects in migraineurs, we performed functional imaging scans on patients treated with erenumab.Methods:We conducted a functional magnetic resonance imaging (fMRI) study on 27 migraine patients, using a well-established trigeminal nociceptive paradigm, examining patients before and two weeks after administration of the CGRP-receptor-antibody erenumab 70 mg.Results:Comparing both visit days in all patients (n=27) revealed that erenumab leads to a decrease in activation in the right thalamus (i.e. contralateral to the stimulated side), right middle temporal gyrus, right lingual gyrus, left operculum, and several clusters on both sides of the cerebellum. Furthermore, when contrasting responders (n=9) and non-responders (n=8) of the respective same headache state, we found a significant reduction of hypothalamic activation after the administration of erenumab in responders only (T-value: 4.78; contrast estimate [90% CI]: 29.79 [19.53; 40.05]). This finding of reduced hypothalamic activation was confirmed when using the absolute headache days as a regressor.Interpretation:These findings suggest that erenumab may not be an exclusively peripheral migraine treatment but has additional central effects. Whether this is due to secondary changes following peripheral modulation of sensory input or indeed represents a direct central mode of action is discussed.

The existence of a trigeminocervical complex has been suggested based on animal data, but only indirect evidence exists in humans. We investigated the functional relationship between the trigeminal and the occipital region by stimulating one region and measuring electrical pain thresholds (EPTs) of the corresponding opposite region. This study consists of 2 single-blinded, randomised protocols. Forty healthy participants were recruited in the propaedeutic protocol I. Electrical pain thresholds were measured on the V1 and the greater occipital nerve (GON) dermatome bilaterally as well as on the left forearm longitudinally before and after application of topical capsaicin. Protocol II was then online preregistered, and, additionally, the ipsilateral trigeminal dermatomes V2 and V3 were tested. Greater occipital nerve stimulation increased the EPT ipsilateral at V1 after 20 minutes (P 5 0.006) compared with baseline, whereas trigeminal stimulation increased the EPT at the ipsilateral (P 5 0.023) as well as the contralateral GON (P 5 0.001) after capsaicin application. Protocol II confirmed these results and additionally showed that GON stimulation with capsaicin increased EPTs ipsilateral at all 3 trigeminal dermatomes and that trigeminal stimulation on V1 led to an ipsilateral increase of EPTs at GON, V2, and V3. Our data suggest a strong functional interplay between the trigeminal and occipital system in humans. The fact that the stimulation of one of these dermatomes increases the EPT of the respective other nerve could be explained by segmental inhibition on the brainstem level.

Die Kieler Arbeiten zur skandinavistischen Linguistik publizieren Arbeitspapiere und Forschungsergebnisse aus der skandinavistischen Linguistik am Institut für Skandinavistik, Frisistik und Allgemeine Sprachwissenschaf der Christian-Albrechts-Universität zu Kiel.