Voluntary wheel exercise reduces pain behavior by modulating neuroinflammation in neuropathic pain

Neuropathic pain (NP) is a common condition caused by injury or disease of the somatosensory nervous system. It is associated with excessive inflammation of the central and peripheral nervous system. The treatment of NP is extremely challenging. In recent years, exercise therapy has received extensive research attention. Voluntary wheel running (VWR) is a simple aerobic exercise commonly used in animal experiments. VWR-induced analgesia seems to be associated with re-establishment of the neuroinflammatory system. This paper discusses the effects of VWR on the inflammatory response of the nervous system, including the brain, spinal cord, dorsal root ganglia (DRG), and peripheral nerves involved in NP regulation. VWR works by decreasing pro-inflammatory cytokines in the brain, spinal cord, DRG, and peripheral nerves, as well as by increasing anti-inflammatory cytokines to show anti-inflammatory effects. VWR also decreases the expression of glial cells in the brain, spinal cord, and DRG and modulates neuroinflammation. This study reviews the mechanisms by which VWR modulates neuroinflammation in NP to reduce pain behaviors and improve our understanding of the VWR role in NP treatment.