**4. Final considerations**

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

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 precursors, aimed at treating diseases or symptomatology that had no effective treatment. Despite of the animal models described for FM, some limitations can be observed, such as the reversion of the pain with opioid treatment and the absence of other signs and symptoms observed in humans. However, these models are the most resembled FM in humans, being tools used in the search for new treatment options. Nowadays, many natural substances have been studied, clinically and preclinically, for their analgesic potential with respect to fibromyalgia. In this context, essential oils, plant extracts, terpenes, and alkaloids are major sources of natural products.

These substances have been shown to have an analgesic effect in animal models of fibromyalgia, acting through different pathways, including activation of the descending inhibitory pain pathway—specifically the opioid, glutamatergic, cannabinoid, and serotoninergic systems; inhibition of SP in the superficial dorsal horn of the spinal cord; blockage of peripheral fibers; and antioxidant activity. In addition, clinical studies have shown the importance of NPs in the pain management of FM, improving their quality of life. The effective use of these products in the clinic, without reports of considerable adverse effects, describes the advances in the use of NPs in the treatment of FM. These finding make natural products a promising source of treatments for the management of chronic pain.
