Specialized, Pro-Resolving Mediators as Potential Therapeutic Agents for Alleviating Fibromyalgia Symptomatology

Abstract

Objective: To present a hypothesis on a novel strategy in the treatment of fibromyalgia (FM).

Design: A narrative review.

Setting: FM as a disease remains a challenging concept for numerous reasons, including undefined etiopathogenesis, unclear triggers, and unsuccessful treatment modalities. We hypothesize that the inflammatome, the entire set of molecules involved in inflammation, acting as a common pathophysiological instrument of gut dysbiosis, sarcopenia, and neuroinflammation, is one of the major mechanisms underlying FM pathogenesis. In this setup, dysbiosis is proposed as the primary trigger of the inflammatome, sarcopenia as the peripheral nociceptive source, and neuroinflammation as the central mechanism of pain sensitization, transmission, and symptomatology of FM. Whereas neuroinflammation is highly considered as a critical deleterious element in FM pathogenesis, the presumed pathogenic roles of sarcopenia and systemic inflammation remain controversial. Nevertheless, sarcopenia-associated processes and dysbiosis have been recently detected in individuals with FM. The prevalence of pro-inflammatory factors in the cerebrospinal fluid and blood has been repeatedly observed in individuals with FM, which supports the idea of a role of the inflammatome in FM pathogenesis. As such, failed inflammation resolution might be one of the underlying pathogenic mechanisms. Accordingly, the application of specialized, inflammation pro-resolving mediators (SPMs) seems most suitable for this goal.

Conclusions: The capability of various SPMs to prevent and attenuate pain has been repeatedly demonstrated in laboratory animal experiments. As SPMs suppress inflammation in a manner that does not compromise host defense, they could be attractive and safe candidates for the alleviation of FM symptomatology, probably in combination with anti-dysbiotic medicine.

Keywords: Chronic Inflammation; Dysbiosis; Fibromyalgia; Sarcopenia; Specialized Pro-Resolving Mediators.