Metabolomics
While the genomics and proteomics suggest a possible mode of operation of the system, metabolomics gives the actual representation of the system. In agreement with the multifactorial nature of the disease, the studies conducted to date relate to different classes of analytes. In fact, several different mechanisms, such as neuro-inflammatory, neurological and cerebrovascular, have so far been suggested in migraine pathophysiology [32].
Whereas the presence of inflammatory processes during migraine attacks, serum levels of different proinflammatory molecules have been investigated. Several studies have found elevated levels of C-Reactive Protein (CRP), a marker of chronic low-grade inflammation, in patients with migraine [33,34]. Also the procalcitonin levels were investigated as indicators of inflammation in migraine patients with and without aura. Turan et al. found significantly high levels of PCT in patients with migraine during the attack compared to the interictal period (0.0485 vs 0.0298 ng/ml) [35]. An interesting fact was found by Guldiken et al. about the increase of soluble CD40 ligand (sCD40L). In this study, sCD40L amount was higher in the subgroup of migraineurs with aura than in those without aura and in rare attacks rather than in the frequent ones. In both comparisons the difference in the levels of sCD40L was not significant but these data may be related to the association of migraine with cardiovascular diseases [36].
Also the correlation between migraine and molecules of pain was investigated. Several observation suggested a relationship between low serum levels of vitamin D and higher incidence of chronic pain [37,38]. However, in a large cross-sectional study, Kjaergaard et al. have found that low level of serum vitamin D were associated with non-migraine type of headache [39]. Further studies should be conducted to clarify the potential association of vitamin D and migraine pain. Brain-derived neurotrophic factor (BDNF) is a neurotrophin associated with pain modulation and central sensitization [40]. Fisher et al. have demonstrated that in migraineurs, BDNF was significantly elevated during migraine attacks (31.24 ± 9.31 ng/ml) compared with headache-free periods (24.50 ± 9.17 ng/ml), tension-type headache (20.97 ± 2.49 ng/ml) and healthy controls (21.20 ± 5.64 ng/ml) [41]. This study, showing a correlation between migraine and BDNF, supports the hypothesis that BDNF has a role in the pathophysiology of migraine. The results are in agreement with a pilot study of Tanure et al. [42].
However, NMR or mass spectrometry techniques are able to provide, with an acceptable probability, the description of the current biochemical state of an organism. The development of proton magnetic resonance spectroscopy (1H-MRS) has been used to assess noninvasively the metabolic status of human brain [43]. Several studies have employed 1H-MRS achieving numerous results for metabolites including N-acetylaspartate (NAA), as a marker of neuronal functioning [44], choline (Cho), as a marker for membrane turnover [45], total creatine (tCr) and lactate, for energy metabolism [46], and myo-inositol (a glial marker) [47]. With the exception of NAA, the results obtained for these molecules are heterogeneous and sometimes contradictory. Indeed the levels of NAA are also increased in the serum [48]. In our opinion, to date, it has not been identified molecules that can be used as a marker for migraine.
Undoubtedly, spectroscopy Nuclear Magnetic Resonance and Mass Spectrometry represent the most powerful and most widely used techniques for the simultaneous analysis of different molecules, allowing together with functional genomics and proteomics to open new roads knowledge in the pathophysiology of migraine. We can suppose that also the progression of the disease may be evaluated by a therapeutic metabolite monitoring approach [49].