Enkephalin and substance P effects related to trigeminal pain

Iontophoretic applications of enkephalin (20-150 nA) reduced the spontaneous firing frequency of nociceptive neurons in the trigeminal nucleus caudalis of decerebrated cats. The response evoked by noxious stimulation (tooth pulp) was gradually inhibited during the 1st minute of application of the opioid and generally remained depressed for 5 min after the current was turned off. These effects of enkephalin were blocked by intravenously or iontophoretically administered naloxone. Nonnociceptive neurons or nociceptive neurons responding to nonnoxious inputs were less frequently inhibited by enkephalin. When tested on nonnociceptive cells, similar applications of substance P usually had little effect. Nociceptive neurons, however, were strongly excited by substance P. This action was not constant and was interrupted by periods of inactivation. Both types of peptide action were similar in temporal aspects. The results suggest a functional interrelationship between enkephalin and substance P in a trigeminal system mediating nociception.