Electrical field stimulation (EFS, 10 V, 50 mA/cm2, 5-50 Hz, 1 ms pulse duration, 10 s train every 20 s for 5 min) produced a rapid and reproducible outflow of calcitonin gene-related peptide like-immunoreactivity (CGRP-LI) from superfused slices from the dorsal half of the rat spinal cord which is abolished by tetrodotoxin (TTX, 0.3-mu-M), in vitro capsaicin desensitization (10-mu-M for 30 min) and in Ca-free medium. The response was unaffected by ruthenium red (10-mu-M), indomethacin (10-mu-M) and nifedipine (1-mu-M) while it was abolished by omega-conotoxin (omega-CTX, 0.1-mu-M) and, in a naloxone-sensitive manner, by morphine (3-mu-M). Since CGRP release from capsaicin-sensitive afferents evoked by EFS in rat peripheral tissues is conotoxin-resistant, these findings provide direct evidence for a qualitative difference between central and peripheral endings of capsaicin-sensitive primary afferents in the mechanisms regulating transmitter release in the same species.