The inhibitory effect of substance P antagonist, CP-96,345, on the late discharges of nociceptive neurons in the rat superficial spinal dorsal horn.

The effects of local spinal applications of the substance P antagonist, CP-96,345, on the electrically-evoked discharges of nociceptive neurons were examined in the superficial spinal dorsal horn of adult rats anesthetized with sodium pentobarbital. Extracellular single-unit recordings were made from lumbar spinal dorsal horn neurons which were excited by noxious mechanical stimulation and had early and late discharges evoked by A- and C-fiber inputs, respectively, following transcutaneous electrical stimulation. CP-96,345 was applied directly onto the surface of the spinal cord close to the recording sites. A dose of 50 nmol of CP-96,345 drastically inhibited the late discharges of 80% of neurons, without affecting early discharges significantly. This study demonstrated the specific inhibitory effect of CP-96,345 on the late discharges of a restricted population of spinal dorsal horn neurons. These results illustrate the important role of substance P in nociceptive transmission mediated by primary afferent C-fibers in normal acute pain.