Morphine inhibits substance P release from peripheral sensory nerve endings.

Tissue levels of substance P (SP) were determined by radioimmunoassay in cat dental pulps after unilateral electrical stimulation of the inferior alveolar nerve. Nerve stimulation (10 V, 10 Hz, 5 ms for 3 min) reduced the SP level at the stimulated side by approximately 40%, indicating a release of SP. Stimulation performed after infusion of morphine (0.3 mg/kg/min, i.v.) for 10 min did not reduce the pulpal SP-level. Naloxone (3 mg/kg, i.v.) administered immediately before the morphine infusion in three experiments, did not influence the effect of morphine on pulpal SP levels after nerve stimulation. This may indicate an action of morphine on a naloxone-insensitive receptor type. Morphine in the dosage used did not influence the intradental sensory nerve conductivity. The results indicate that morphine is able to inhibit stimulus evoked release of SP from peripheral endings of primary afferent neurons.