The prevalence of FM has been evaluated in many studies around the world. The mean prevalence in the general population is 2.7 % (4.1 % in female and 1.4 % in male), with a female-to-male ratio of 3:1 [2]. In 2015, however, in a prevalence study comparing the three ACR criteria [1, 3, 4], Jones et al. [7] showed that FM prevalence rates vary with the different sets of classification criteria applied, being higher with the ModACR2010. In population studies, the mean 1-year prevalence of headache in general is 46 %, migraine 11 %, and tension-type headache (TTH) 42 % [11].

Some studies have estimated the prevalence of FM in patients with primary headache, especially migraine. The prevalence rates of FM in some primary headaches are shown in Table 5.2. FM is highly prevalent, both in migraineurs and in patients with TTH. The mean prevalence of FM in migraine patients in these nine studies is 19.4 % (Table 5.2).

The prevalence of headache in patients with FM has also been estimated. Marcus, Bernstein, and Rudy [21] reported that 76 % of FM patients complained of headache; 63 % of them had migraines. Vij et al. [22] found 55.8 % of migraine in FM sufferers.

Recent studies in primary headache patients sharing FM comorbidity indicated that this comorbidity involves prevalently chronic tension-type headache and chronic migraine. Many studies focused on selected groups of migraine patients [12, 13], whereas in studies conducted on larger cohorts of primary headache patients, only migraine and tension-type headache seemed prone to this association, while other forms of primary headache, as cluster headache, did not show a relevant presence of patients with diffuse pain [15]. Among primary headache patients, frequency of headache, anxiety, pericranial tenderness, sleep disorders, and low physical quality of life were indicated as the main symptoms predisposing to FM comorbidity [15]. In other studies on episodic migraine, high headache frequency was not indicated as a common feature of FM comorbidity [19], but evaluations were conducted in smaller case series not including chronic migraine. Moreover, also in those episodic migraine groups, severe headache intensity typified FM patients [19]. Another still unclear point is the low representation of FM symptoms among patients with migraine with aura [15]. In most of the studies, groups of migraine with aura included few patients [13, 14, 16, 19] in agreement with the lower frequency of this type of migraine in the general population. The reason why we did not find FM comorbidity in pure migraine with aura patients may be the low frequency of attacks in those patients, while patients with associated migraine without aura or evolving into chronic form showed FM-associated symptoms [15]. This observation, though worth further assessment in lager series, may confirm that frequency of headache is an important factor predisposing to FM comorbidity in migraine and tension-type headache groups. In other headache syndromes, such as chronic forms of TACs, FM was rarely represented, suggesting that these headache types probably do not have pathophysiological factors predisposing to widespread pain. Features of sleep were also described in a recent study of our group [23], showing that the reduced quantity of sleep as assessed by the MOS scale was associated with frequent and invalidating migraine, though patients with FM comorbidity presented with a more complex sleep disturbance, including deterioration of sleep quality and severe sleep disorders.

The general impression emerging from these studies is that the identification of features of FM comorbidity in primary headache patients includes the assessment of headache frequency, pericranial tenderness, quality of life, anxiety scores, and sleep features, which may be easily obtained in a routine clinical examination, as detailed below.

The common mechanism concurring in migraine, tension-type headache, and fibromyalgia is a dysfunction of pain modulation with enhanced expression of central sensitization symptoms [24, 25].

Sensitization is a physiological phenomenon of the sensory system, which supports a progressive amplification of sensory neuron activation under repetitive stimulation, favoring the development of memory against potentially dangerous events by neuroplastic changes enabling a prompt defensive response. This phenomenon develops at both peripheral and central levels, given that increased excitability occurs in single neurons and at synaptic level. In neuropathic pain, where a lesion occurs at peripheral or central level [26], increased excitability of sensory neurons has a compensatory function and is determined as soon as the neuronal tissue is damaged. The natural evolution of any kind of persisting noxious stimulation leads to the progressive increase in sensory sensitization, contrasted by the modulation of the descending control, which is very complex and finalized to the adaptation of the subjective sufferance to the general context, cognitive and emotional status, and cultural trends [27]. In addition, brain structural or functional changes may influence the outcome of the descending modulation [27]. Allodynia, which determines an innocuous tactile and mechanoreceptive stimulus to be perceived as painful, is a clinical sign of central sensitization, indicating a change in the function of second-order wide-range sensory neurons in spinal cord and trigeminal nucleus. This symptom is present in both migraine and FM. Since many years, studies by Burstein group [28] ascertained an early development of allodynia during migraine attack, causing the skin and muscles to become painful in the pericranial and even somatic level. The spreading of pain outside the pericranial sites indicates sensitization at third-order thalamic-sensory neuron level [29]. In tension-type headache, pericranial tenderness is initially subtended by different causes, as postural problems, but symptoms persist for a central dysmodulation, which does not inhibit but rather enhances primary and secondary nociceptive neurons firing and the consequent muscular activation [30]. So far, allodynia and pericranial tenderness are symptoms of central sensitization which can predispose primary headache patients to diffuse somatic pain. In fact, in FM, pain at tender points is evoked by an innocuous mechanic stimulation and is provoked by sensitization of second-order nociceptive neurons in the spinal cord [25]. Migraine and FM are characterized by a predisposition to central sensitization as suggested by neurophysiological evidence. In fact, habituation of the sensory system, which is a physiological phenomenon occurring during repetitive stimulation to contrast the progressive increase of neuronal activation, is lacking in both migraine and FM syndrome, with special regard to nociceptive input processing [6, 31, 32]. New evidence about an involvement of the peripheral nervous system in the pathogenesis of pain in FM is opening a new scenario on this very complex syndrome and associated conditions. Skin biopsy findings suggested a dysfunction of small myelinated and unmyelinated afferents, which may be a phenotypical feature peculiar for FM [33, 34].