• Azize Boström, Dirk Scheele, Birgit Stoffel-Wagner, Frigga Hönig, Shafqat R Chaudhry, Sajjad Muhammad, Rene Hurlemann, Joachim K Krauss, Ilana S Lendvai, Krishnan V Chakravarthy, and Thomas M Kinfe.
• Department of Neurosurgery, University Hospital Bonn, Bonn, Germany.
• J Transl Med. 2019 Feb 22; 17 (1): 53.

BackgroundRising evidence indicate that oxytocin and IL-1β impact trigemino-nociceptive signaling. Current perspectives on migraine physiopathology emphasize a cytokine bias towards a pro-inflammatory status. The anti-nociceptive impact of oxytocin has been reported in preclinical and human trials. Cervical non-invasive vagus nerve stimulation (nVNS) emerges as an add-on treatment for the preventive and abortive use in migraine. Less is known about its potential to modulate saliva inflammatory signaling in migraine patients. The rationale was to perform inter-ictal saliva measures of oxytocin and IL-1ß along with headache assessment in migraine patients with 10 weeks adjunctive nVNS compared to healthy controls.Methods12 migraineurs and 12 suitably matched healthy control were studied with inter-ictal saliva assay of pro- and anti-neuroinflammatory cytokines using enzyme-linked immuno assay techniques along with assessment of headache severity/frequency and associated functional capacity at baseline and after 10 weeks adjunctive cervical nVNS.ResultsnVNS significantly reduced headache severity (VAS), frequency (headache days and total number of attacks) and significantly improved sleep quality compared to baseline (p < 0.01). Inter-ictal saliva oxytocin and IL-1β were significantly elevated pre- as well as post-nVNS compared to healthy controls (p < 0.01) and similarly showed changes that may reflect the observed clinical effects.ConclusionsOur results add to accumulating evidence for a therapeutic efficacy of adjunct cervical non-invasive vagus nerve stimulation in migraine patients. This study failed to provide an evidence-derived conclusion addressed to the predictive value and usefulness of saliva assays due to its uncontrolled study design. However, saliva screening of mediators associated with trigemino-nociceptive traffic represents a novel approach, thus deserve future targeted headache research. Trial registration This study was indexed at the German Register for Clinical Trials (DRKS No. 00011089) registered on 21.09.2016.

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