Schematic of SPM biosynthesis and the actions of SPMs in the control of inflammation, neuroinflammation, pathological pain and itch. SPMs (resolvins, protectins, maresins, and lipoxins) are primarily biosynthesized from omega-3 poly-unsaturated fatty acids (Omega-3 PUFA, including EPA and DHA) and Omega-6 PUFA (arachidonic acid) via different lipoxygenase (LOX) and cyclooxygenase (COX) enzymes. SPM production is facilitated by neuromodulation, such as vagus nerve stimulation, spinal cord stimulation, and electroacupuncture, sham surgery, and acute inflammation.