Morphine attenuates surgery-induced enhancement of metastatic colonization in rats

Gayle Giboney Page, Shamgar Ben-Eliyahu, Raz Yirmiya, John C. Liebeskind*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

152 Scopus citations


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.

Original languageAmerican English
Pages (from-to)21-28
Number of pages8
Issue number1
StatePublished - Jul 1993

Bibliographical note

Funding Information:
This researchw as supportedb y a Oncology Nursing Foundation/Purdue Frederick Research Grant, the UCLA Program in Psychoneuro immunology, NIH Grant NS07628, and an Unrestricted Pain Research Grant from the Bristol-Myers Squibb Company. We appreciatet he excellentc are given to our animalsb y Mr. Herbert Washingtona nd his Vivarium staff.


  • Immunity
  • MADB106
  • Metastasis
  • Morphine analgesia
  • Natural killer cells
  • Surgery


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