Fig. 3.

Neuromodulation, such as VNS, spinal cord stimulation, deep brain stimulation, transcranial magnetic stimulation (TMS), transcutaneous nerve stimulation (TENS), and electroacupuncture (EA), promotes resolution of chronic pain via producing SPMs (e.g., RvD1). SPMs act on their receptors that are expressed on immune cells, glial cells, and neurons. Through SPM receptor signaling in different cell types, SPMs powerfully control inflammation and neuroinflammation, leading to pain relief and cognitive improvement after major surgeries, trauma, and infection. A combination of dietary supplements, such as fish oil and neuromodulation, may result in additive or synergistic beneficial effects by boosting the production of SPMs