MORPHINE ATTENUATES SURGERY-INDUCED ENHANCEMENT OF METASTATIC COLONIZATION IN RATS

Painful stressors such as surgery have been shown both to suppress imm une function and to enhance tumor development. Whether the immune syst em mediates the tumor-enhancing effects of surgery remains unclear. Mo reover, the role of postoperative pain has been largely ignored in suc h studies. To explore these issues, we used the MADB106 tumor, a mamma ry adenocarcinoma syngeneic to the subjects of this study (Fischer 344 rats) and known to be sensitive to natural killer (NK) cell activity. We found that surgery enhanced metastatic colonization and that this tumor-enhancing effect occurred only during the time in which the MADB 106 tumor is sensitive to NK control. These results support the hypoth esis that suppression of NK cell activity mediates the surgery-induced enhancement of metastatic colonization. Further, we found that an ana lgesic dose of morphine blocked the surgery-induced increase in metast asis without affecting metastasis in unoperated animals. These finding s suggest that postoperative pain is a critical factor in promoting me tastatic spread. If a similar relationship between pain and metastasis occurs in humans, then pain control must be considered a vital compon ent of postoperative care.