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 duration. Here, we demonstrate SP- and NKA-mediated excitatory postsynaptic currents (EPSCs) in dorsal horn neurons of young rats using whole-cell patch-clamp recording techniques. After complete blockade of glutamate receptor-mediated currents, we observed a small residual EPSC. The residual EPSCs exhibited temporal summation in response to a train of stimulation (six pulses delivered 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 terminals; SP and NKA pretreatment; NK(1) or NK(2) receptor antagonists; and inhibition of postsynaptic G proteins. EPSCs were neither blocked by a metabotropic 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 present study provides electrophysiological evidence that suggests the possible contribution of SP and NKA to sensory synaptic transmission between primary afferent fibers and dorsal horn neurons.
Li
P
P
Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
Zhuo
M
M
D015763:2-Amino-5-phosphonovalerate / Q000378:metabolism; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000367:Age Factors; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020865:Calcium Channels, P-Type / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D015288:Neurokinin A / Q000494:pharmacology*; D010146:Pain / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010721:Phosphinic Acids / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013873:Thionucleotides / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D020865:Calcium Channels, P-Type; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D017470:Receptors, Glutamate; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D013873:Thionucleotides; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D006153:Guanosine Diphosphate; C085075:CGP 55845A; D013373:Substance P; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C023427:guanosine 5'-O-(2-thiodiphosphate); D015763:2-Amino-5-phosphonovalerate; D015288:Neurokinin A; D020866:omega-Conotoxin GVIA