Buprenorphine ameliorates the effect of surgery on hypothalamus-pituitary-adrenal axis, natural killer cell activity and metastatic colonization in rats in comparison with morphine or fentanyl treatment

Brain Behav Immun. 2007 Aug;21(6):767-74. doi: 10.1016/j.bbi.2007.01.001. Epub 2007 Feb 8.


Not all opioids employed in clinical practice share the same immunosuppressive properties. The potent partial micro-agonist buprenorphine appears to exhibit a neutral effect on the immune responses. Surgery stress is associated with decreased natural killer cell activity (NK) and enhancement of tumor metastasis in rats. We analyzed the ability of buprenorphine to prevent the effects of experimental surgery on HPA activation (plasma corticosterone levels), NK activity and lung diffusion of the NK sensitive tumor MADB106. Buprenorphine (0.1mg/kg) was compared with equianalgesic doses of fentanyl (0.1mg/kg) and morphine (10mg/kg) in this animal model. In normal animals morphine and fentanyl stimulate the HPA axis, decrease NK activity and augment tumor metastasis, while buprenorphine is devoid of these effects. Surgery significantly raised corticosterone levels, suppressed NK activity and increased MADB106 metastasis. Only buprenorphine was able to prevent the neuroendocrine and immune system alterations and ameliorate the increase of tumor metastasis induced by surgical stress. These preclinical findings suggest that an adequate treatment of surgically induced stress immunosuppression with an opioid drug devoid of immunosuppressive effects may also play a protective role against the metastatic diffusion following cancer surgery.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / immunology
  • Analgesics, Opioid / pharmacology*
  • Analysis of Variance
  • Animals
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology*
  • Buprenorphine / immunology
  • Buprenorphine / pharmacology*
  • Corticosterone / blood
  • Disease Models, Animal
  • Fentanyl / adverse effects
  • Fentanyl / immunology
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • Immune Tolerance / drug effects*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Laparotomy / adverse effects
  • Lung Neoplasms / immunology
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary*
  • Male
  • Morphine / adverse effects
  • Morphine / immunology
  • Neoplasm Metastasis
  • Neoplasms, Experimental / immunology
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism
  • Rats
  • Rats, Inbred F344
  • Stress, Physiological / etiology
  • Stress, Physiological / immunology*


  • Analgesics, Opioid
  • Buprenorphine
  • Morphine
  • Fentanyl
  • Corticosterone