Specialized Pro-resolving Lipid Mediators: A New Class of Non-immunosuppressive and Non-opioid Analgesic Drugs

We now appreciate that the mechanism of resolution depends on an active and time-dependent biosynthetic shift from pro-inflammatory to pro-resolution mediators, the so-called specialized pro-resolving lipid mediators (SPMs). These SPMs are biosynthesized from the omega-3 fatty acids arachidonic acid (AA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), or docosahexaenoic acid (DHA). Despite effective for a fraction of patients with rheumatic diseases and neuropathic pain, current analgesic therapies such as biological agents, opioids, corticoids, and gabapentinoids cause unwanted side effects, such as immunosuppression, addiction, or induce analgesic tolerance. A growing body of evidence demonstrates that isolated SPMs show efficacy at very low doses and have been successively used as therapeutic drugs to treat pain and infection in experimental models showing no side effects. Moreover, SPMs work as immunoresolvents and some of them present long-lasting analgesic and anti-inflammatory effects (i.e. block pain without immunosuppressive effects). In this review, we focus on how SPMs block pain, infection and neuro-immune interactions and, therefore, emerge as a new class of non-immunosuppressive and non-opioid analgesic drugs.