Abstract text (incl. figure legends and references)

Objective: Peripheral sensitization consisting of reduction of Pressure Pain Threshold (PPT) is related to migraine. Aim of this study was to investigate the neurophysiological effect of anti-CGRP monoclonal antibodies (mAbs) on PPT as modulation of peripheral sensitization in migraineurs.

Methods: An observational cohort study in migraineurs without aura treated with anti-CGRP mAbs was performed. Type and doses of anti-CGRP mAbs were chosen by a headache expert. All patients underwent a PPT analysis, conducted according to the Andersen"s standardized guidelines of the PPT assessment over craniofacial muscles. We tested five muscles of the trigemino-cervical-complex and one far from this area. PPT values of all muscles of each area were measured at baseline (t0) and after 3 (t1) and 4 (t2) months after the first injection of the anti-CGRP mAb. Data were compared with PPT in healthy controls. Data were analysed with GraphPad InStat 3.06.

Results: Eleven migraineurs and 11 healthy controls (mean age 43±15; F=63.6%) were enrolled. Patients were diagnosed as high-frequency episodic migraine (45.5%) or chronic migraine (54.5%), and they were treated with erenumab 140 mg (63.6%), fremanezumab (27.3%) or galcanezumab (9.1%). All migraine outcomes improved at t1 and t2 (migraine days/month: 18.2±6.9 t0 vs 8±4.7 t1 vs 6.1±3.8 t2; severe hours/month: 28.1±40.7 t0 vs 1.6±2.9 t1 vs 3.7±5.6 t2; MIDAS: 100±25 t0 vs 21±15.4 t1). At t0, migraineurs showed a significant lower PPT respect to controls in all muscles, except in the left temporalis and procerus. PPT increased in all migraineurs" muscles at t1 and t2 without significant differences between migraineurs and healthy controls.

Conclusion: High-frequency episodic migraine and chronic migraine have lower PPT in cephalic and extra-cephalic muscles compared to healthy controls. Treatment with anti-CGRP mAbs normalizes migraineurs" PPT, that is related to the improvement of headache.