Speaking out of turn: A role for silent synapses in pain

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.