Publication Type:Journal Article
Source:Proc Natl Acad Sci U S A, Volume 88, Issue 24, p.11344-8 (1991)
Keywords:Animals, Biphenyl Compounds, Cats, Evoked Potentials, Ganglia, Spinal, Neurons, Nociceptors, Pain, Receptors, Neurokinin-1, Receptors, Neurotransmitter, Spinal Cord, Substance P, Synapses, Time Factors, Touch
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.