Chronic pain is the primary symptom of
osteoarthritis affecting a patient's quality of life.
Neuroinflammation and oxidative stress in the spinal cord contribute to arthritic
pain and represent ideal targets for
pain management. In the present study, a model of
arthritis was established by
intra-articular injection of complete
Freund's adjuvant (CFA) into the left knee joint in mice. After CFA inducement, knee width and
pain hypersensitivity in the mice were increased, motor disability was impaired, spinal inflammatory reaction was induced, spinal astrocytes were activated,
antioxidant responses were decreased, and
glycogen synthase kinase 3β (GSK-3β) activity was inhibited. To explore the potential therapeutic options for arthritic
pain,
lycorine was intraperitoneally injected for 3 days in the CFA mice.
Lycorine treatment significantly reduced mechanical
pain sensitivity, suppressed spontaneous
pain, and recovered motor coordination in the CFA-induced mice. Additionally, in the spinal cord,
lycorine treatment decreased the inflammatory score, reduced
NOD-like receptor protein 3
inflammasome (NLRP3) activity and IL-1β expression, suppressed astrocytic activation, downregulated NF-κB levels, increased nuclear factor erythroid 2-related factor 2 expression and
superoxide dismutase activity. Furthermore,
lycorine was shown to bind to GSK-3β through three electrovalent bonds, to inhibit GSK-3β activity. In summary,
lycorine treatment inhibited GSK-3β activity, suppressed NLRP3
inflammasome activation, increased the
antioxidant response, reduced spinal
inflammation, and relieved arthritic
pain.