**5. Conclusions**

Our results provide evidence that a combined treatment of melatonin and folic acid may be useful in the treatment of fibromyalgia, thanks to its ability to target all mediators that contribute to the perpetuation of pain, from the mastocytosis and related pro-inflammatory, vasoactive and neuro-sensitizing mediators to the oxidative stress processes.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2076-3921/8/12/628/s1, Figure S1: E fficacy of folic acid and melatonin administration on behavioral changes of sham groups, Figure S2: <sup>E</sup>fficacy of folic acid and melatonin administration on oxidative stress of sham groups, Figure S3: E fficacy of folic acid and melatonin administration on nitrityrosine and PARP expression of sham groups, Figure S4: E fficacy of folic acid and melatonin administration on mast cells activation of sham groups, Figure S5: E fficacy of folic acid and melatonin administration on IL-1β, TNF-<sup>α</sup>, VEGF and NGF expression of sham groups, Figure S6: E fficacy of folic acid and melatonin administration on Iba1 and CD11b expression of sham groups.

**Author Contributions:** Conceptualization, S.C. and R.D.P.; Methodology, D.I.; Software, M.C.; Validation, M.C., R.S. and E.G.; Formal Analysis, R.C.; Investigation, A.F.P.; Resources, R.F.; data curation, R.D.; writing original draft preparation, R.F.; writing—review and editing, R.D.P.; visualization, E.G.; supervision, R.D.P.; project administration, S.C.; funding acquisition, S.C.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.
