Figure 1

Excitatory sensory synapses contribute to pain transmission in the spinal dorsal horn and ACC. A. Synaptic currents recorded at resting membrane potentials are mostly mediated by AMPA receptors (a), some synaptic currents at dorsal horn neurons receiving high-threshold inputs are mediated by KA receptors (b). In young and adult dorsal horn neurons, some sensory synapses are 'silent' and containing only functional NMDA receptors (c). These pure NMDA synapses can be revealed when cells are hold at positive 40 mV potentials. In adult dorsal horn neurons, some pure NMDA receptor synapses can even be detected at the resting membrane potentials. When a train of stimulation is applied, neuropeptide mediated responses are recruited. Both postsynaptic NK1 and NK2 receptors contribute to substance P(SP)- and neurokinin A- (NKA) mediated excitatory postsynaptic currents. In ACC neurons, KA receptor mediated responses are detected with stimulation at greater intensities. KA receptors do not contribute to mEPSCs, indicating that KA receptors are not co-expressed with AMPA receptors in all synapses. B. Models for glutamate-containing and glutamate- and neuropeptide-mixed sensory synapses in the spinal cord dorsal horn and possible ACC neurons. At least four different synapses are found: (a) synapses receiving low-threshold sensory inputs contain only postsynaptic NMDA receptors; (b) synapses receiving low-threshold sensory inputs contain both AMPA and NMDA receptors; (c) synapses receiving both low- and high-threshold sensory inputs contain postsynaptic AMPA, KA and NMDA receptors; (d) synapses receiving low- and high-threshold sensory inputs contain AMPA, KA and NMDA receptors as well as peptidergic NK1 and NK2 receptors.