**Acknowledgements**

FM diagnosis was confirmed before the patients enrolled in the study. The authors reveal that the main mode of action is as a counterirritant to the pain sensation. The mixture of oils promotes stimulation of A-beta sensory fibers, causing inhibition of the A-delta and C fibers. Moreover, the local effects of O24™ include the inhibition of bradykinin, histamine, and prostaglandins, which do not seem to be directly related to the analgesic effect in FM, so it is more

Rutledge and Jones [86] also investigated the topical effect of O24 in a double-blind randomized clinical trial associated with exercises multilevel for 12 weeks. Twenty patients with FM and 23 patients of the sham group were submitted to the study. There was no statistical difference between the groups regarding the pain and physical function, but there was improvement of the physical function, without statistical difference, when compared before and after the treatment, keeping the effect of O24 on the FM symptoms unknown. This result for O24 differs from that described by Ko et al. [26], which may result from the small sample and the type of exercise used, since some exercises may contribute to the maintenance of pain in patients with FM [3].

The effect of *Ginkgo biloba* extract and the coenzyme Q10 was evaluated in 23 fibromyalgic patients, before and after the treatment, by oral administration, for 12 weeks, with 64% of patients reporting an improvement in quality of life through the application of questionnaires. The improvement observed by these patients may be related in parts to the antioxidant

Due to the properties attributed to capsaicin, Casanueva et al. [34] evaluated the short-term efficacy of topical capsaicin treatment in 130 patients with fibromyalgia who were already using drug therapy. Patients were randomly divided into a control group (same medical treatment that they received before randomization) and topical capsaicin group (medical treatment that they received before randomization + 0.075% capsaicin) by a computer-generated sequence. After 6 weeks, it was observed that the additional topical treatment reduced the myalgia score and improved the quality of life of these patients, showing that capsaicin

Fibromyalgia is the second most common rheumatologic disorder, being characterized by the manifestation of widespread pain with sensory changes. The treatment strategies for the management of the FM include both pharmacological products (such as duloxetine, pregabalina, and tramadol for pain and amitriptyline, cyclobenzaprine, and pregabalina for sleep disturbance) and non-pharmacological therapies (such as exercise and psychological therapies) [87]. Despite this, fibromyalgia remains difficult to treat and is an important challenge for modern medicine, as the treatments for these conditions are still ineffective with a large

In this context, one important approach to the discovery of new medicines with analgesic activity is research with natural products. For thousands of years, scientists and the pharmaceutical industry have used natural products as a source for new drugs or their

number of side effects, making the search for new treatments ever more urgent.

reasonable to propose its effect indirectly in the pathways of pain modulation.

activities described for both coenzyme Q10 and *Ginkgo biloba* [28].

was also effective in this syndrome.

70 Discussions of Unusual Topics in Fibromyalgia

**4. Final considerations**

This work was supported by grants from CNPq (305608/2013-4, 311721/2014-1), CAPES, and FAPITEC/SE (Chamadas Públicas PROMOB e PROEF), all from Brazil. PL Santos, RG Brito, and MA Oliveira were carrying out the master's or PhD degrees in the Graduate Program in Health Sciences (PPGCS/UFS), and LTS Pina was carrying out the master's degree in the Graduate Program in Pharmaceutical Sciences (PPGCF/UFS).
