Figure 2.

Nociceptive-induced changes in the trafficking of spinal AMPAR (neuronal level) cause a broken balance between synaptic excitation and inhibition that leads to overall hyper-excitability and central sensitization of the DH (network level); aberrant signaling in central pain pathways turns pain chronic (systemic level). Various scenarios for targeting the broken GluA1 and/or GluA2 recycling can be implemented to suppress the AMPAR-mediated nociceptive plasticity, and recover the relative balance between neuronal excitation and inhibition in the DH circuits, thereby alleviating chronic pain