Physiopathology, Diagnosis and Therapy of Primary Cephalalgia and Adaptive Disorders
Physiopathology, Diagnosis and Therapy of Primary Cephalalgia and Adaptive Disorders
The main aim of the present pilot study is to prove the possibility to use the Nitroglycerin
 (NTG) model to describe the pathophysiology of headache using task-free advanced Magnetic
 Resonance Imaging (MRI) techniques, in order to depict the static changes of the ictal and
 inter-ictal phase of migraine attacks vs the pain free state in healthy subjects and to
 compare that with the spontaneous headache attack experienced by chronic migraineurs.
Resting state functional magnetic resonance imaging (rs-fMRI) has depicted cyclical
 functional connectivity changes during the ictal and inter-ictal phase of the migraine
 attack. In this pilot study, Functional Connectivity (FC) changes during nitroglycerin (NTG)
 induced migraine attacks were assessed vs the pain-free condition in healthy subjects.

 To this end, subjects with episodic migraine (EM) without aura were enrolled. NTG-triggered a
 spontaneous-like migraine attack in the subjects. They underwent 4 rs-fMRI scan repetitions
 during different phases of the attack (baseline, prodromal, full blown, recovery phase) with
 a 3 Tesla MR scanner. According to the pain field literature, several regions of interests
 were studied, in particular the thalamic areas and the salience network (SN) were selected as
 primary areas of interest for the analyses. Subjects' rs-fMRI data were first processed with
 a seed-based correlation analysis (SCA) to assess the static changes in FC between the
 thalamus and the rest of the brain during the experiment. The wavelet coherence approach
 (WCA) were also applied to test the changes in time-in-phase coherence between the thalamus
 and the salience network (SN).

 Healthy subject were administered nitroglycerin as well and scanned at a pain free baseline
 and after 3 hours in order to compare the response.

 The rebound headache that followed acute drug withdrawal were used as a surrogate paradigm of
 spontaneous attack. Patients with chronic migraine and medication overuse were hospitalized
 for a supervised withdrawal program at the Mondino Foundation; during the program if they
 experienced a rebound headache attack, they were scanned with a rs-fMRI acquisition.

 The acquired imagines were analyzed with the same procedure regarding the evaluation of
 static and dynamic functional connectivity fluctuation.
Episodic migraineurs

 Inclusion Criteria:

 -  age between 18-60 years;

 -  diagnosis of episodic migraine without aura developed before the age of 50;

 -  no current prophylactic treatment for migraine prevention;

 -  chronic migraineurs with medication overuse according to the ICHDIII criteria

 Exclusion Criteria:

 -  chronic or medication-overuse headache or cluster headache diagnosis;

 -  any chronic pain condition or disorders other than migraine;

 -  an alleged diagnosis of major psychiatric disorders such as depression, bipolar
 affective disorder and schizophrenia;

 -  a diagnosis of tension type headache with a frequency of more than 5 days per month;

 -  any cardiovascular diseases in which the NTG use could be contraindicated;

 -  blood pressure hypotension, closed angle glaucoma, anaemia;

 -  women in child bearing, breast feeding; continuous use of benzodiazepines;

 -  any neuroradiological pathological findings at a previous MRI scan of the head.

 Chronic migraineurs

 Inclusion Criteria:

 -  age between 18-60 years;

 -  diagnosis of migraine without aura developed before the age of 50 according to the
 ICHD III criteria;

 -  currently chronic migraineurs with medication overuse according to The International
 Classification of Headache Disorders 3rd edition (ICHDIII) criteria.

 Exclusion Criteria:

 -  any chronic pain condition or disorders other than migraine;

 -  an alleged diagnosis of major psychiatric disorders such as depression, bipolar
 affective disorder and schizophrenia;

 -  a diagnosis of tension type headache with a frequency of more than 5 days per month;

 -  any cardiovascular diseases in which the NTG use could be contraindicated;

 -  blood pressure hypotension, closed angle glaucoma, anaemia; women in child bearing,
 breast feeding;

 -  continuous use of benzodiazepines;

 -  any neuroradiological pathological findings at a previous MRI scan of the head.

 Healthy subjects

 Inclusion Criteria:

 -  age between 18-60 years;

 -  overall good clinical condition, no neurological findings at the physical examination.

 Exclusion criteria:

 -  history of episodic or chronic or medication-overuse headache or cluster headache
 diagnosis according to the International Chronic Headache Disease (ICHD) III criteria;

 -  any chronic pain condition or disorders other than migraine;

 -  an alleged diagnosis of major psychiatric disorders such as depression, bipolar
 affective disorder and schizophrenia;

 -  a diagnosis of tension type headache with a frequency of more than 5 days per month;

 -  any cardiovascular diseases in which the NTG use could be contraindicated;

 -  blood pressure hypotension, closed angle glaucoma, anaemia;

 -  women in child bearing, breast feeding;

 -  continuous use of benzodiazepines;

 -  any neuroradiological pathological findings at the baseline MRI scan of the head.