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

Neuroscience
V Radhakrishnan, J L Henry

Abstract

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 affe...Continue Reading

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Citations

Aug 22, 2001·Biological Psychiatry·N Haddjeri, P Blier
Jan 1, 1997·Inflammatory Bowel Diseases·M ReinshagenV E Eysselein
May 1, 1996·The European Journal of Neuroscience·N VibertM Muhlethaler
Dec 31, 1997·The European Journal of Neuroscience·V Radhakrishnan, J L Henry
Mar 20, 2014·Pain Management·Hafiz Hassan, David A Walsh
Oct 1, 1996·The Journal of Orthopaedic and Sports Physical Therapy·K A Sluka
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·A ZimmerE Mezey
Jan 23, 2016·Journal of Pharmacological Sciences·Shohei YamamotoMasahiro Ohsawa
Nov 3, 2005·The European Journal of Neuroscience·Reza Sharif NaeiniJames L Henry
Mar 17, 2006·Journal of Neurochemistry·V S SeyboldP G Mermelstein

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