Novel substance P antagonist, CP-96,345, blocks responses of cat spinal dorsal horn neurons to noxious cutaneous stimulation and to substance P.

Responses of dorsal horn neurons to iontophoretic application of substance P (80-120 nA), and to noxious thermal and noxious mechanical stimulations of the receptive field in the hind limb were tested in adult cats before and after the administration of the specific, non-peptide, NK-1 receptor antagonist CP-96,345 (0.5 mg/kg, i.v.). CP-96,345 inhibited the response of the neurones to substance P and also the response of these substance P-sensitive neurones to noxious thermal stimulation. The response of the substance P-insensitive neurones to noxious heat stimulations were, however, unaffected by CP-96,345. The effect of CP-96,345 on the response of neurones to noxious mechanical stimulation was variable. The results confirm the role of substance P in thermal nociception.