Ketamine stimulates secretion of beta-endorphin from a mouse pituitary cell line.

BACKGROUND AND OBJECTIVES: beta-endorphin is an endogenous opioid that mediates pain-induced analgesia. Propofol inhibits in vitro secretion of beta-endorphin from a mouse pituitary cell line (AtT-20). We hypothesized that ketamine would also alter secretion of beta-endorphin. METHODS: AtT-20 cells were exposed to the intravenous anesthetic ketamine (10 to 40 micromol/L). Secretion of beta-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 beta-endorphin. AtT-20 cells were stimulated with secretagogues to induce secretion of beta-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 beta-endorphin to levels that were up to 3 times greater than baseline secretion. Stimulation of beta-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 micromol/L ketamine. CONCLUSIONS: Clinically relevant concentrations of ketamine stimulated both immediate and delayed secretion of beta-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.

The effects of femoral nerve blockade in conjunction with epidural analgesia after total knee arthroplasty.

Either epidural analgesia or femoral nerve blockade improves analgesia and rehabilitation after total knee arthroplasty. No study has evaluated the combination of femoral nerve blockade and epidural analgesia. In this prospective, randomized, blinded study we investigated combining femoral nerve blockade with epidural analgesia. Forty-one patients received a single-injection femoral nerve block with 0.375% bupivacaine and 5 microg/mL epinephrine; 39 patients served as controls. All patients received combined spinal-epidural anesthesia and patient-controlled epidural analgesia with 0.06% bupivacaine and 10 microg/mL hydromorphone. Average duration of epidural analgesia was 2 days. All patients received the same standardized physical therapy intervention. Median visual analog scale (VAS) scores with physical therapy were significantly lower for 2 days among patients who received a femoral nerve block versus controls: 3 versus 4 (day 1), 2.5 versus 4 (day 2); P < 0.05. Median VAS pain scores at rest were 0 in both groups on days 1 and 2. Flexion range of motion was improved on postoperative day 2 (70 degrees versus 63 degrees ; P < 0.05). No peripheral neuropathies occurred. We conclude that the addition of femoral nerve blockade to epidural analgesia significantly improved analgesia for the first 2 days after total knee arthroplasty.

Inhibition by propofol of intracellular calcium mobilization in cultured mouse pituitary cells.

UNLABELLED: Propofol inhibited regulated secretion of the neuropeptide beta-endorphin from AtT-20 cells, a pituitary tumor cell line. Neuropeptide secretion depends on an increase of intracellular calcium (Ca(2+)) levels. We investigated the hypothesis that propofol altered intracellular Ca(2+) levels in AtT-20 cells. Propofol (100 microM) did not inhibit Ca(2+)-induced secretion of beta-endorphin from digitonin-permeabilized cells. Thus, propofol did not inhibit neuropeptide secretion by blocking the effects of increased intracellular Ca(2+). Intracellular Ca(2+) was measured in intact cells using a Ca(2+)-sensitive dye. Ca(2+) transients were generated by depolarization with KCl or by incubation with thapsigargin (an inhibitor of Ca(2+) uptake into the endoplasmic reticulum). Propofol inhibited generation of Ca(2+) transients in intact cells by KCl (half-maximal inhibitory concentration of 14.9 microM; P < 0.05). Nitrendipine also inhibited potassium-induced Ca(2+) peaks. Propofol 50 microM reduced the thapsigargin-induced Ca(2+) peak to 47% of control (P < 0.05). Thapsigargin-induced Ca(2+) peaks were not affected by calcium channel blockade by nitrendipine. Propofol inhibited the stimulus-induced increase in intracellular Ca(2+). Propofol inhibited thapsigargin-induced Ca(2+) transients, but nitrendipine did not, indicating that propofol had effects on intracellular Ca(2+) independent of blockade of L-type Ca(2+) channels. Propofol may inhibit release of Ca(2+) from intracellular stores. These results are consistent with the hypothesis that propofol inhibits neuropeptide secretion by inhibiting the stimulus-induced increase in intracellular Ca(2+). IMPLICATIONS: Propofol may block both entry of calcium into cells and release of calcium from intracellular stores, thereby inhibiting regulated secretion of neuropeptides. Study of the effects of propofol on intracellular calcium metabolism may increase understanding of how propofol alters brain function and may aid development of better IV anesthetics.