The proposed project aims at establishing Calcitonin gene-related peptide (CGRP)-Related Axon Reflex of Trigeminal Afferents as a neurophysiological biomarker for migraine.

The proposed project aims at establishing a neurophysiological biomarker for migraine. Migraine is one of the world's most disabling diseases and its prophylactic treatment is time and cost-consuming. Since each patient responds differently and unpredictably to preventive medication, physicians are forced to try prophylactic drugs one by one. Recently, a new group of therapeutic agents targeting the neuropeptide Calcitonin gene-related peptide (CGRP) has been launched for migraine treatment. CGRP is stored in trigeminal afferents and released to meningeal blood vessels during acute migraine attacks leading to a vasodilating response. In an experimental setting, the release of CGRP from afferent nerve fibers in the skin can be induced by transdermal electrical stimulation. The subsequently evoked skin erythema, called 'flare reaction', can be quantified by laser Doppler imaging techniques. Never before, research studies used this experimental model in either trigeminally innervated skin or migraine patients. I therefore propose to establish this model to 1) test the specificity of an evoked 'flare response' in the trigeminal territory for the pathophysiology of migraine, 2) investigate the effect of CGRP-targeting anti-migraine drugs on this outcome parameter and 3) evaluate the impact of this model to predict the treatment response to drugs interfering with the CGRP-pathway. This study is a highly innovative approach towards tailored migraine treatment.

Inclusion Criteria:

Healthy volunteers (Study Arm 1 and 2):

• age ≥ 18 years
• good German language skills
• no history of head trauma
• no history of neurologic disease
• no primary headache disorder (e.g. migraine, episodic or chronic tension type headache, cluster headache)
• no regular drug intake (except for oral contraceptives)

Migraine patients need to match the following criteria (Study Arm 2 and 3):

• age ≥ 18 years
• good German language skills
• fulfilling the diagnostic criteria for either episodic or chronic migraine with or without aura according to the international classification of headache disorders (ICHD) 3rd edition
• history of migraine > 1 year
• keeping a headache diary for a minimum of 3 months prior to the study

Exclusion Criteria:

Healthy volunteers and migraine patients under the following conditions will be excluded:

• Chronic pain syndromes (e.g. low back pain, osteoarthritis, painful neuropathy, rheumatoid arthritis)
• Acute pain (e.g. pain due to acute skin injury, menstrual pain, acute toothache). In this case, a measurement can only be performed after complete remission of pain and at least 48 hours after intake of acute pain medication (e.g. triptans, non-steroidal anti-inflammatory drug (NSAID)).
• history of treatment with agents targeting the CGRP pathway (e.g. erenumab) < 3 months before the study
• history of treatment with Botulinum toxin < 9 months before the study
• Diseases of the skin involving the skin at face and forehead
• Pregnancy or breast feeding
• Subjects lacking capacity for consent