Morphine attenuates surgery-induced enhancement of metastatic colonization in rats

Pain. 1993 Jul;54(1):21-28. doi: 10.1016/0304-3959(93)90095-7.


Painful stressors such as surgery have been shown both to suppress immune function and to enhance tumor development. Whether the immune system mediates the tumor-enhancing effects of surgery remains unclear. Moreover, the role of postoperative pain has been largely ignored in such studies. To explore these issues, we used the MADB106 tumor, a mammary 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 MADB106 tumor is sensitive to NK control. These results support the hypothesis that suppression of NK cell activity mediates the surgery-induced enhancement of metastatic colonization. Further, we found that an analgesic dose of morphine blocked the surgery-induced increase in metastasis without affecting metastasis in unoperated animals. These findings suggest that postoperative pain is a critical factor in promoting metastatic spread. If a similar relationship between pain and metastasis occurs in humans, then pain control must be considered a vital component of postoperative care.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / physiopathology*
  • Adenocarcinoma / secondary
  • Anesthesia
  • Animals
  • Behavior, Animal / drug effects
  • Feeding Behavior / drug effects
  • Flow Cytometry
  • Killer Cells, Natural / immunology
  • Lung Neoplasms / etiology
  • Male
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / physiopathology*
  • Mammary Neoplasms, Experimental / secondary
  • Morphine / therapeutic use*
  • Pain, Postoperative / physiopathology*
  • Rats
  • Rats, Inbred F344
  • Tumor Cells, Cultured


  • Morphine