Chronic pain (CP) is a severe clinical entity with devastating physical and emotional consequences for patients, which can occur in a myriad of diseases. Often, conventional treatment approaches appear to be insufficient for its management. Moreover, considering the adverse effects of traditional analgesic treatments, specialized pro-resolving lipid mediators (SPMs) have emerged as a promising alternative for CP. These include various bioactive molecules such as resolvins, maresins, and protectins, derived from ω-3 polyunsaturated fatty acids (PUFAs); and lipoxins, produced from ω-6 PUFAs. Indeed, SPMs have been demonstrated to play a central role in the regulation and resolution of the inflammation associated with CP. Furthermore, these molecules can modulate neuroinflammation and thus inhibit central and peripheral sensitizations, as well as long-term potentiation, via immunomodulation and regulation of nociceptor activity and neuronal pathways. In this context, preclinical and clinical studies have evidenced that the use of SPMs is beneficial in CP-related disorders, including rheumatic diseases, migraine, neuropathies, and others. This review integrates current preclinical and clinical knowledge on the role of SPMs as a potential therapeutic tool for the management of patients with CP.

Endocrine and Metabolic Diseases Research Center School of Medicine University of Zulia Maracaibo 4004 Venezuela

Escuela de Nutrición y Dietética Facultad de Medicina Universidad Andres Bello Santiago 8370035 Chile

Facultad de Ciencias de la Salud Universidad Simón Bolívar Barranquilla 080002 Colombia

Institute of Molecular and Translational Medicine Palacký University Olomouc 77900 Olomouc Czech Republic

Programa de Psicología Fundación Universitaria del Área Andina sede Valledupar Valledupar 200001 Colombia

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Costenbader K.H. Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Knee Pain. [(accessed on 10 July 2021)];2021 Available online: clinicaltrials.gov.

University of North Carolina Chapel Hill Pilot, Double-Blind, Randomized Controlled, Multi-Center Study of the Effects of Fish Oil and Vitamin D in the Prevention of Chronic Pain Following Major Thermal Burn Injury. [(accessed on 10 July 2021)];2020 Available online: clinicaltrials.gov.

Swisse Wellness Pty Ltd. A Randomised, Double-Blind, Placebo Controlled Study to Investigate the Effect on Knee Pain Reduction and Safety of Swisse High Strength Deep Sea Krill Oil (Superba BOOST) in Adults with Mild to Moderate Osteoarthritis of the Knee. [(accessed on 10 July 2021)];2020 Available online: clinicaltrials.gov.

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