Substance P and neurokinin A mediate sensory synaptic transmission in young rat dorsal horn neurons

Spinal nociceptive transmission is mediated by glutamate and neuropeptides such as substance P (SP), and neurokinin A (NKA). The neuropeptide-mediated excitatory postsynaptic potentials (EPSPs) had a slow onset and long durat ion. Here, we demonstrate SP- and NKA-mediated excitatory postsynaptic curr ents (EPSCs) in dorsal horn neurons of young rats using whole-cell patch-cl amp recording techniques. After complete blockade of glutamate receptor-med iated currents, we observed a small residual EPSC. The residual EPSCs exhib ited temporal summation in response to a train of stimulation (six pulses d elivered at 10-50 Hz). High intensity stimulation (the same or greater than the stimulation threshold for nociceptive fibers in vivo) was required for evoking these summated EPSCs. Summated EPSCs were attenuated or abolished by capsaicin pretreatment, which depletes SP and NKA from presynaptic termi nals; SP and NKA pretreatment; NK1 or NK2 receptor antagonists; and inhibit ion of postsynaptic G proteins. EPSCs were neither blocked by a metabotropi c glutamate receptor antagonist nor a gamma -aminobutyric acid(B) receptor antagonist. The summated EPSCs were also sensitive to voltage-gated calcium channel antagonists or mu -opioid receptor activation by DAMGO. The presen t study provides electrophysiological evidence that suggests the possible c ontribution of SP and NKA to sensory synaptic transmission between primary afferent fibers and dorsal horn neurons. (C) 2001 Elsevier Science Inc.