Analgesia and ptosis caused by caerulein and cholecystokinin octapeptide (CCK-8)

Subcutaneous injection of caerulein and C-terminal octapeptide of cholecystokinin (CCK-8) produced in mice sedation, palpebral ptosis and a decrement in response to noxious stimulation (analgesia) in the hot-plate and the writhing test, but not in the tail-flick test. Pentagastrin was inactive. Both analgesia and ptosis occurred within 5–10 min, peaked by 15min and lasted about 60 min. On a molar basis, caerulein was, on the hot plate, 114 times and in the writhing test, 15 times more potent than morphine. Cholecystokinin was 3–10 times less active than caerulein. Low doses of naloxone nullified the analgesic effect but left ptosis intact. Tolerance to morphine had only negligible influence on the analgesic response, and enhanced the ptosis. A possible peripheral (intestinal) component of the mechanism of action could be excluded.