Fibromyalgia (FM) is the second most common rheumatologic disorder, affecting 5% of the world population, and has a serious effect on the quality of life of patients, as well as an economic impact through lost workdays. This pain syndrome is a common cause of chronic widespread pain and is characterized by reduced pressure pain thresholds with hyperalgesia and allodynia, nonrestorative sleep, fatigue, cognitive dysfunction, and mood disturbances. The pharmacological treatment strategies for FM include the use of antidepressants, calcium channel modulators, muscle relaxants, and analgesics but have shown limited efficacy and therapeutic adherence. Thus, researchers have been seeking potential substances (new chemical entities or through drug repositioning) that could be used for FM treatment. In this context, natural products (NPs) have been shown to be promising pharmacological tools due to the variety of their pharmacological activity and the number of molecular sites available as possible active targets. Recent clinical and preclinical studies have been conducted to verify the possible applicability of NPs such as essential oils (EOs), plants extracts, terpenes, sapogenins, and alkaloids in the treatment of FM. The results have shown that natural products have an analgesic effect in different animal models of FM, probably by activation of inhibitory descending pathways, such as the periaqueductal gray and rostroventromedial medulla. Natural products and their secondary metabolites could therefore be a promising source for FM management. However, translational studies that seek to validate the preclinical studies are scarce, incipient, and lacking an approach focused on the traditional pharmaceutical market.
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