A comparison of the analgesic and gastrointestinal transit effects of [D-Pen², L-Cys⁵] enkephalin after intracerebroventricular and intrathecal administration to mice

Intrathecal (i.t.) administration of the highly delta selective peptide, [D-Pen², L-Cys⁵]enkephalin (DPLCE) (1-10 μg), effectively inhibited gastrointestinal transit of an orally-given radiolabelled marker in mice. By contrast, the same doses did not affect marker transit after intracerebroventricular (i.c.v.) administration. I.c.v. or i.t. administration of the peptide effectively increased the latency to hindpaw lick using the 55° C hot-plate as the nociceptive stimulus. Maximum analgesic effects were seen with 0.3 μg given i.t. or 10 μg given i.c.v. Time-response studies showed activity for as long as 20 min after administration by either route. The differential gastrointestinal effects of DPLCE after i.c.v. and i.t. administration to mice suggest that delta receptors in the brain may mediate analgesic but not gut effects while spinal cord receptors may be less functionally selective.