The nursing care of individuals recovering from surgery prominently includes pain management. Nurses are key in influencing pain medication choices and in providing pain medication to individuals. The objective of the research proposed in this application is to explore the immunosuppressive and tumor-enhancing effects of surgery, and the attenuation of these consequences by managing perioperative pain. The 4 specific aims are: (1) to explore the impact of morphine preparation and administration schedules on surgery-induced enhancement of metastasis in adult males; (2) to investigate the impact of surgery on natural killer (NK) cell activity in preadolescent females and males, and to compare the magnitude of this effect with that observed in adult males; (3) to study the effect of surgery on metastasis in preadolescent females and males, and to compare the magnitude of this effect with that observed in adult males; and (4) to explore the impact of morphine on surgery-induced enhancement of metastasis in preadolescent females and males, and to compare these outcomes with adult males. To investigate these issues, the MADB106 tumor cell line, a mammary adenocarcinoma syngeneic to the inbred Fischer 344 rats to be studied, will be used. After intravenous injection, the metastasis of these tumor cells in the lungs is controlled by NK function, which models what is known about metastasis in humans and also provides an index of NK activity in the whole organism. All surgery animals will undergo an experimental laparotomy shown to both suppress NK cytotoxic activity and promote the metastasis of MADB106 tumor cells. Perioperative morphine administration has been shown to attenuate the increase in metastasis resulting from surgery. In order to discern the most efficacious schedule of pain-relieving drug administration, groups of animals will receive morphine either pre- or postoperatively, or both, and the retention of tumor cells in the lungs will be assessed. Given that NK cell activity has been shown to be markedly less in very young children compared to adults, it is important to know whether this vulnerable population is more susceptible to the NK-suppressive effects of surgery; and, if so, whether perioperative pain management is efficacious in ameliorating these effects, as has been observed in adults. The findings of this proposed research have the potential to empower health care providers with additional knowledge upon which to base pain-relieving medication administration strategies for optimizing outcomes from surgery.