"These findings provide further support to our supposition that unmanaged pain is associated with potentially life-threatening consequences," says Page. "If our results in animals prove to be similar in humans, controlling postoperative pain and inflammation must become a priority in the management of cancer patients undergoing surgery," she adds.
Prior research in animals has shown that pain and surgical trauma suppress the immune system's natural killer (NK) cells, trigger an inflammatory response and significantly increase tumor development.
Page and her co-investigator at Tel Aviv University reasoned that the relatively strong anti-inflammatory action of indomethacin would therefore affect postoperative tumor growth.
"We have already tested other pain relievers, such as morphine and fentanyl, and shown that they provide some protection against the tumor-promoting effects of surgery, but these drugs are pain relievers without anti-inflammatory action," Page says. "So we chose to test indomethacin because it eases both pain and inflammation and is injectable, giving us control in its administration."
In the study, 124 anesthetized rats, without a tendency to grow tumors, were subjected to surgery, given indomethacin, and injected with cancer cells. After surgery, female rats had an overall 200 percent increase in lung tumor growth, and tumor growth in males increased by 350 percent. Two doses of indomethacin (either 1.5mg or 4.0 kg) reduced the tumor development in both males and females by up to 63 percent. The scientists also found that rats undergoing surgery showed suppressed NK activity, which was restored after receiving indomethacin. Rats of both sexes that got indomethacin also exhibited behavior suggesting abdominal discomfort was relieved.
The study was funded by the National Institute of Nursing Research at the National Institutes of Health. Shamgar Ben-Eliyahu, of the Tel Aviv University Department of Psychology, was also an author and supported by the National Cancer Institute at the National Institutes of Health.
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