Ibuprofen elevates immunoreactive β-endorphin levels in humans during surgical stress

Release of β-endorphin is modulated by physiologic stress and a variety of hormonal and pharmacologic factors. Prostaglandin E₂ inhibits release of β-endorphin and corticotropin from pituitary corticotroph cells, suggesting that suppression of prostaglandin levels should increase β-endorphin release. This hypothesis was tested by administration of 600 mg ibuprofen before surgical stress in humans in comparison to placebo and methylprednisolone. Plasma samples were analyzed for immunoreactive β-endorphin with concurrent measurement of pain and apprehension. Levels of immunoreactive β-endorphin increased during surgery in the placebo group but were significantly greater in the group of patients pretreated with ibuprofen. Methylprednisolone suppressed intraoperative immunoreactive β-endorphin, compared with both placebo and ibuprofen. Parallel in vivo and in vitro studies indicate that nonsteroidal antiinflammatory drug potentiation of endorphin release is mediated at the level of the pituitary corticotroph cell. These results show that ibuprofen enhances pituitary release of β-endorphin by corticotroph cells in response to stress.