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

Gregory Livshits, Alexander Kalinkovich*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations


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.

Original languageEnglish
Pages (from-to)977-990
Number of pages14
JournalPain Medicine
Issue number5
StatePublished - 1 May 2022


FundersFunder number
Ariel University Research & Development Department2000000457
Israel Science Foundation2054/19


    • Chronic Inflammation
    • Dysbiosis
    • Fibromyalgia
    • Sarcopenia
    • Specialized Pro-Resolving Mediators


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