Postoperative demand for analgesics in relation to individual levels of endorphins and substance P in cerebrospinal fluid

Fourteen adult patients were allowed to self-administer small intravenous doses of pethidine to relieve postoperative pain. Thirteen of the patients obtained subjectively satisfactory analgesia while establishing steady-state levels of pethidine in plasma. The individual demand for pethidine was related to individual levels of fraction I endorphins and substance P-like immunoreactivity in the cerebrospinal fluid (CSF). There was a significant and inverse relationship between preoperative fraction I concentrations in CSF and the individual mean pethidine concentrations in plasma ( P < 0.05) and CSF ( P < 0.02) during self-administration. In the 24 h period encompassing surgery and postoperative self-administered analgesia, substance P decreased in 7 patients with calculated CSF pethidine > 200 ng/ml, but remained virtually unchanged in 7 patients with calculated CSF pethidine < 200 ng/ml. The results suggest a role for endorphins in the modulation of acute pain and are compatible with experimental evidence for an inhibitory effect of opiates on substance P release.