Cannabinoid-mediated glial modulation in chronic pain

Chronic pain affects over 30% of people globally, costing the US $560-635 billion annually. Driven by maladaptive plasticity, chronic pain involves neuroinflammatory and synaptic changes in regions such as the spinal cord, thalamus, hippocampus, and periaqueductal gray (PAG). The endocannabinoid system (ECS), including endocannabinoids (AEA, 2-AG), receptors (CB1Rs, CB2Rs, GPR55, TRPV1), and enzymes (FAAH, MAGL), modulates pain via neuronal and glial mechanisms. Microglia and astrocytes exhibit ECS alteration, influencing inflammation and pain relief.