Fibromyalgia Syndrome (FMS) is a chronic pain condition whose prevalence in the general population ranges from 4 to 7 %, with a net female predominance [
1,
2]. According to the 1990 ACR criteria, the syndrome is diagnosed if 2 main conditions are fulfilled: 1) presence of diffuse musculoskeletal pain of at least 3 months’ duration and 2) positivity of at least 11 out of 18 predetermined body sites (9 symmetrical) called tender points (TePs), i.e., tenderness for an applied standard pressure of 4 kg-f exerted either manually or via a pressure algometer [
3]. These criteria were revised in 2010 [
4], with preliminary new criteria no longer taking into account the TeP count, while introducing more clinical requisites in addition to the diffuse muscle pain, e.g., the presence of sleep disorders, affective dysfunction, headache or visceral pains [
5‐
9]. FMS has, indeed, a high degree of comorbidity with a number of other medical conditions, among which headache, especially with an elevated number of attacks or chronic, is particularly frequent [
10,
11]. Though tension-type headache is the most prevalent type in FMS, there is also a high co-occurrence between the syndrome and migraine [
12]. A recent large epidemiologic study, in fact, evidenced a 55.8 % prevalence of migraine among fibromyalgia patients [
13], while other studies showed the prevalence of fibromyalgia in migraine patients to be over 30 % [
14,
15]. Although the pathophysiology of FMS is still incompletely known, a crucial role in the syndrome is believed to be played by central mechanisms of sensitization, secondary to an imbalance of neuromediators involved in nociceptive transmission/control in the Central Nervous System (CNS), in genetically predisposed subjects [
16-
18]. Clinical evidence of sensitization is provided by the generalized decrease in pain thresholds to different modalities of stimuli at somatic level not only in spontaneous painful areas but also in control, nonpainful sites, which has been widely documented in the syndrome [
6,
19,
20]. High frequency and chronic headache have also been found to display increased sensitivity to pain in somatic areas outside the cephalic region, although to a lesser extent with respect to fibromyalgia [
21‐
28]. These observations have raised the question as to whether the association of FMS with headache involves higher degrees of central sensitization with respect to one condition only. Clinical observations also report that FMS patients with concurrent headache, particularly migraine, often present an exacerbation of their typical FMS symptomatology in concomitance with or immediately subsequent to a headache attack, suggesting that headache may represent a triggering factor for fibromyalgia pain. However, in spite of the high degree of co-occurrence between headache and fibromyalgia, no systematic studies appear to have been conducted so far to evaluate the implications of this co-morbidity not only for the spontaneous FMS symptoms but also for the general sensory asset of the patients. This kind of study is instead important not only to better investigate the underlying mechanisms of these chronic pain co-morbidities, but also for therapeutic purposes, as the specific treatment of one condition could have a significant impact upon the symptoms of the other. On this basis, the aim of the present study was to verify: firstly, if the association of FMS with migraine involves different levels of pain hypersensitivity with respect to one condition only; secondly if, in co-morbid patients, the hypersensitivity level is a function of migraine frequency; thirdly, if migraine attacks act as a triggering factor for FMS symptoms. Quantitative sensory tests were carried out in both painful and nonpainful sites and the correlation was explored between occurrence and frequency of migraine attacks and fibromyalgia exacerbations (flares). In addition, the effects were investigated of reducing migraine frequency via specific prophylaxis, on the degree of FMS pain and hyperalgesia.