Substance P-mediated slow excitatory postsynaptic potential elicited in dorsal horn neurons in vivo by noxious stimulation.
The original proposal that substance P is involved in the regulation of nociceptive information at the first sensory synapse in the spinal cord has been substantiated by a wide range of evidence, but definitive support has been lacking, due primarily to the lack of evidence that a specific nociceptive response in the dorsal horn can be blocked by a substance P antagonist. Here, we present evidence that CP-96,345, a specific substance P (NK-1) receptor antagonist, selectively blocks a slow, prolonged excitatory postsynaptic potential following noxious cutaneous stimulation or a train of intense electrical stimuli to sensory nerves but does not affect the response to innocuous input or the brief response to single electrical stimuli to C fibers. These results indicate the specific involvement of substance P in the mediation of a prolonged after-excitation to noxious stimulation. This may have important implications for the etiology and treatment of chronic pain and for plastic changes in nociceptive pathways.
De Koninck
Y
Y
Department of Physiology, McGill University, Montréal, Québec, Canada.
Henry
J L
JL
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002415:Cats; D005071:Evoked Potentials / Q000187:drug effects; D005727:Ganglia, Spinal / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology* / Q000503:physiopathology; D013373:Substance P / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014110:Touch
D001713:Biphenyl Compounds; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; C066892:CP 96345