The effects of tramadol and morphine on immune responses and pain after surgery in cancer patients

Anesth Analg. 2000 Jun;90(6):1411-4. doi: 10.1097/00000539-200006000-00028.


There has been growing interest in determining the possible immune consequences of opioid administration for the management of postoperative pain. We studied the effects of morphine and tramadol on pain and immune function during the postoperative period in 30 patients undergoing abdominal surgery for uterine carcinoma. Phytohemoagglutinin-induced T lymphocyte proliferation and natural killer cell activity were evaluated immediately before and after surgery, and 2 h after the acute administration of either 10 mg of morphine IM or 100 mg tramadol IM for pain. In all patients, phytohemagglutinin-induced lymphoproliferation was significantly depressed by surgical stress. However, in the morphine-treated group, proliferative values remained lower than basal levels for 2 h after treatment, whereas in tramadol-administered patients proliferative values returned to basal levels. Natural killer cell activity was not significantly affected by surgery nor by morphine administration, whereas tramadol significantly enhanced the activity of natural killer cells. Both drugs produced a comparable reduction in postoperative pain. We conclude that, as previously observed in the experimental animal, tramadol and morphine, when administered in analgesic doses, induce different immune effects.

Implications: Recent studies suggest that opioids can have an adverse impact on the immune system. Because surgical stress also induces immune dysfunction, the search for analgesic drugs devoid of immunosuppressive effects is of import. This study compared the effects on immune responses of morphine and of the atypical opioid analgesic, tramadol, given for postoperative pain to gynecological cancer patients. Tramadol and morphine showed comparable analgesic activity; however, tramadol, in contrast to morphine, induced an improvement of postoperative immunosuppression and, therefore, may be preferred to morphine for the treatment of postoperative pain.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Analgesics, Opioid / adverse effects*
  • Analgesics, Opioid / therapeutic use*
  • Chromium Radioisotopes
  • Female
  • Humans
  • Immunity / drug effects*
  • Immunity, Cellular / drug effects
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Male
  • Middle Aged
  • Morphine / adverse effects*
  • Morphine / therapeutic use*
  • Pain Measurement
  • Pain, Postoperative / drug therapy*
  • Phytohemagglutinins / pharmacology
  • Postoperative Period
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Tramadol / adverse effects*
  • Tramadol / therapeutic use*
  • Uterine Neoplasms / complications*
  • Uterine Neoplasms / surgery*


  • Analgesics, Opioid
  • Chromium Radioisotopes
  • Phytohemagglutinins
  • Tramadol
  • Morphine