Figure 2: Activated glial cell produces neuroactive mediator and responds to neuroactive mediator with special references to NO. Glial cell is activated by inflammatory mediator, bacteria, virus, and nerve injury. Nerve injury produces ATP from presynaptic neuron and activates glial cell. NO comes from pos tsynaptic neuron in persistent pain state and activates glia through MAPK activation (Figure 1). Activated glia reduces uptake of glutamate, increasing synaptic glutamate concentration, intensifying pain. IL-1,IL-6, TNFα,INFγ,and gp120 induces NO production via NOS with subsequent increase in IL-1,IL-6, TNFα,INFγ, and PGE2, working on itself, neighboring glia and neurons with autocrine and paracrine manner. ATP, adenosine triphosphate; COX, cyclooxygenase; cGMP, cyclic guanosine monophosphate; CR, cytokine receptor; GCR, G-protein coupled receptor; IL, interleukin; INF, interferon; MAPK, mitogen-activated protein kinase; NOS, nitric oxide synthase(inducible, neuronal, endothelial); NO, nitric oxide; PGE, prostaglandin E; P2X, ionotropic purinoceptor; P2, ionotropic purinoceptor(P2X) or G-protein-coupled pyrimidinergic receptor(P2Y); ROS, reactive oxygen species; TLR, Toll-like receptor; TNF, tumor necrosis factor;