Opiate analgesics inhibit substance P release from rat trigeminal nucleus

Abstract

THE undecapeptide substance P (SP) may act as a transmitter released from the terminals of primary sensory nerves in the spinal cord1–2. SP has been shown to be highly concentrated in the terminals of small diameter fibres in the substantia gelatinosa of the dorsal horn in mammalian spinal cord, and these terminals disappear after dorsal root section3–6. Sensory nuclei of some of the cranial nerves, such as the spinal trigeminal nucleus, also contain a high density of SP nerve terminals6–7. SP is released by a calcium-dependent mechanism from the isolated rat spinal cord during electrical stimulation of the dorsal roots8. The peptide is also a powerful excitant of neurones in the spinal cord2, and seems to excite selectively those cells in dorsal horn that respond to noxious stimuli9–10. SP may, therefore, represent the excitatory transmitter, or one of the transmitters, released from primary fibres involved in the transmission of pain. We have examined the stimulus-evoked release of SP from rat spinal trigeminal nucleus slices in vitro to explore the factors which may control its release from primary sensory terminals. We report here that opiate analgesics are able to suppress the stimulus-evoked release of SP. These findings may represent a mechanism for the direct spinal analgesic actions of opiates.