Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
|
pubmed:dateCreated |
1995-6-21
|
pubmed:abstractText |
Extracellular and intracellular studies were undertaken to test the effects of the non-peptide, substance P (NK-1) receptor antagonists CP-96,345 and CP-99,994, and of CP-96,344, the inactive enantiomer of CP-96,345, on the responses of spinal dorsal horn neurons to peripheral noxious and non-noxious cutaneous stimuli in spinalized cats anesthetized with alpha-chloralose. The effect of these agents on the response of dorsal horn neurons to iontophoretic application of substance P was also tested in extracellular studies. The substance P-induced slow, prolonged discharge of dorsal horn neurons was blocked by administration (0.5 mg/kg, i.v.) of CP-96,345 (n = 10) or CP-99,994 (n = 9), but was unaffected by CP-96,344 (n = 9). The response of substance P-sensitive neurons to noxious thermal stimulation of the cutaneous receptive field, especially the late afterdischarge phase, was also significantly inhibited by CP-96,345 (n = 10) and by CP-99,994 (n = 7). The response of such neurons to noxious pinch stimulation of the receptive field was also significantly inhibited by CP-96,345 (n = 7) and CP-99,994 (n = 8), but the response of three other substance P-sensitive neurons to pinch was unaffected by CP-96,345. CP-96,344 did not affect the response of any neuron tested to either of these noxious stimuli (noxious thermal, n = 7; pinch, n = 6). The response to hair afferent stimulation was unaffected by any of these compounds (CP-96,345, n = 16; CP-96,344, n = 5; CP-99,994, n = 6). In intracellular studies, the effect of these antagonists was tested on responses of dorsal horn neurons to noxious pinch stimulation or to a train of high intensity electrical stimulation of the superficial peroneal nerve. Both stimuli produced an initial fast depolarization followed by a slow and prolonged depolarization with corresponding discharge patterns. CP-96,345 (n = 3) and CP-99,994 (n = 6) selectively blocked the late, slow components of the stimulus-evoked response without affecting the early components. Responses to single electrical pulses of the same intensity and duration were not affected. CP-96,344 did not affect any of the responses tested (n = 5). The data indicate that nociceptive responses of a subset of spinal dorsal horn cells are selectively blocked by the NK-1 receptor antagonists, CP-96,345 and CP-99,994, thus confirming the involvement of NK-1 receptors in these responses.(ABSTRACT TRUNCATED AT 400 WORDS)
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-(2-methoxybenzylamino)-2-phenylpip...,
http://linkedlifedata.com/resource/pubmed/chemical/Biphenyl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/CP 96345,
http://linkedlifedata.com/resource/pubmed/chemical/Hypnotics and Sedatives,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurokinin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Substance P
|
pubmed:status |
MEDLINE
|
pubmed:month |
Feb
|
pubmed:issn |
0306-4522
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
64
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
943-58
|
pubmed:dateRevised |
2010-4-29
|
pubmed:meshHeading |
pubmed-meshheading:7538641-Animals,
pubmed-meshheading:7538641-Biphenyl Compounds,
pubmed-meshheading:7538641-Cats,
pubmed-meshheading:7538641-Hot Temperature,
pubmed-meshheading:7538641-Hypnotics and Sedatives,
pubmed-meshheading:7538641-Membrane Potentials,
pubmed-meshheading:7538641-Nociceptors,
pubmed-meshheading:7538641-Piperidines,
pubmed-meshheading:7538641-Receptors, Neurokinin-1,
pubmed-meshheading:7538641-Spinal Cord,
pubmed-meshheading:7538641-Spinal Nerve Roots,
pubmed-meshheading:7538641-Substance P
|
pubmed:year |
1995
|
pubmed:articleTitle |
Antagonism of nociceptive responses of cat spinal dorsal horn neurons in vivo by the NK-1 receptor antagonists CP-96,345 and CP-99,994, but not by CP-96,344.
|
pubmed:affiliation |
Department of Physiology, McGill University, Montreal, Quebec, Canada.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|