Fig. 7. A proposed model of the early (synaptically mediated) events in the spinal cord causing allodynia after L5–L6 spinal nerve ligation. Glutamate, released from the central terminals of primary afferent fibers beginning immediately after ligation, activates postsynaptic NMDA receptors. Subsequent intracellular events (omitted for clarity), including an increase in the Ca²⁺concentration and activation of PLA², trigger the early synthesis of spinal prostaglandins by constitutive activity (cyclooxygenase-1 > cyclooxygenase-2). In the extracellular space, spinal prostaglandins diffuse to adjacent cells to enhance glutamate release and cell excitability (postsynaptic effect). Sustained NMDA receptor activation initiates the delayed expression of inducible cyclooxygenase-2 in the spinal cord (dashed arrow ). Within 24 h of ligation, central sensitization, combined with the enhanced capacity for prostaglandin synthesis (cyclooxygenase-2 > cyclooxygenase-1), results in the emergence of temporary, prostaglandin-dependent allodynia. In the next few weeks (dotted arrow ), prostaglandin-dependent allodynia recedes and leaves long-term allodynia independent of spinal prostaglandins. This may reflect phenotypic changes in primary afferents, sprouting of primary afferents into the outer laminae, altered gene regulation, and changes in expression of critical receptors, ion channels, or enzymes.