Background and Objectives β-endorphin is an endogenous opioid that mediates pain-induced analgesia. Propofol inhibits in vitro secretion of β-endorphin from a mouse pituitary cell line (AtT-20). We hypothesized that ketamine would also alter secretion of β-endorphin.

Methods AtT-20 cells were exposed to the intravenous anesthetic ketamine (10 to 40 μmol/L). Secretion of β-endorphin was determined by enzyme-linked immunosorbent assay. Long-term effects were determined by exposing the cells to ketamine, allowing the cells to recover overnight, then stimulating the secretion of β-endorphin. AtT-20 cells were stimulated with secretagogues to induce secretion of β-endorphin. The effect of ketamine on stimulated secretion was determined. Cultures of AtT-20 cells were grown for 5 days in the presence of ketamine. Cell numbers were determined on each day.

Results Ketamine increased secretion of β-endorphin to levels that were up to 3 times greater than baseline secretion. Stimulation of β-endorphin secretion by ketamine persisted into the subsequent day. Ketamine caused increased secretion from cells stimulated with secretagogues. Ketamine was not toxic to these cells; AtT-20 cells grew normally for 5 days in the presence of up to 40 μmol/L ketamine.

Conclusions Clinically relevant concentrations of ketamine stimulated both immediate and delayed secretion of β-endorphin. This suggests that the prolonged analgesia observed in some clinical situations with ketamine could be in part caused by increased release of an endogenous opioid. Reg Anesth Pain Med 2003;28:12-16.