Severe tissue or nerve injury can result in a chronic and inappropriate sen
sation of pain, mediated in part by the sensitization of spinal dorsal horn
neurons to input from primary afferent fibers. Synaptic transmission at pr
imary afferent synapses is mainly glutamatergic, Although a functioning exc
itatory synapse contains both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepro
prionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the postsy
naptic membrane, recent evidence suggests that dorsal horn neurons contain
some "silent" synapses, which exhibit purely NMDA receptor-mediated evoked
postsynaptic currents and do not conduct signals at resting membrane potent
ial. Serotonin, which is released onto dorsal horn neurons by descending fi
bers from the rostroventral medulla, potentiates sensory transmission by ac
tivating silent synapses on those neurons, i.e., by recruiting functional A
MPA receptors to the postsynaptic membrane. This phenomenon may contribute
to the hyperexcitability of dorsal horn neurons seen in chronic pain condit
ions.