title: The analgesic drug tramadol prevents the effect of surgery on natural killer cell activity and metastatic colonization in rats.
abstract: Surgery stress has been shown to be associated in rat with decreased natural killer (NK) cell activity and enhancement of tumor metastasis. We have previously shown that the analgesic drug tramadol stimulates NK activity both in the rodent and in the human. In the present study, we analyze, in the rat, tramadol ability to prevent the effect of experimental surgery on NK activity and on the enhancement of metastatic diffusion to the lung of the NK sensitive tumor model MADB106. The administration of tramadol (20 and 40 mg/kg) before and after laparatomy significantly blocked the enhancement of lung metastasis induced by surgery. In contrast, the administration of 10 mg/kg of morphine was not able to modify this enhancement. The modulation of NK activity seemed to play a central role in the effect of tramadol on MADB106 cells. In fact, both doses of tramadol were able to prevent surgery-induced NK activity suppression, while the drug significantly increased NK activity in normal non-operated animals. Morphine, that in normal rats significantly decreased NK cytotoxicity, did not prevent surgery-induced immunosuppression. The good analgesic efficacy of tramadol combined with its intrinsic immunostimulatory properties suggests that this analgesic drug can be particularly indicated in the control of peri-operative pain in cancer patients.
authors.affiliation: Department of Pharmacology, University of Milan, via Vanvitelli 32, 20129, Milan, Italy.
authors.forename: Leda
authors.initials: L
authors.lastname: Gaspani
authors.forename: Mauro
authors.initials: M
authors.lastname: Bianchi
authors.forename: Elena
authors.initials: E
authors.lastname: Limiroli
authors.forename: Alberto E
authors.initials: AE
authors.lastname: Panerai
authors.forename: Paola
authors.initials: P
authors.lastname: Sacerdote
mesh_terms: D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007813:Laparotomy / Q000009:adverse effects*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000276:immunology* / Q000517:prevention & control; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013312:Stress, Physiological / Q000276:immunology* / Q000503:physiopathology; D014147:Tramadol / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000759:Adjuvants, Anesthesia; D000701:Analgesics, Opioid; D014147:Tramadol; D009020:Morphine; D010424:Pentobarbital