Chronic fentanyl or buprenorphine infusion in the mouse: similar analgesic profile but different effects on immune responses.
It is known that morphine has a negative impact on the immune responses. The potent opioids fentanyl and buprenorphine have recently become available as transdermal preparation for the treatment of chronic pain. We analyze the effect of fentanyl and buprenorphine on splenic cellular immune responses in the mouse. The parameters evaluated were lymphoproliferation, natural killer cell activity and interleukin-2 and interferon-gamma production. Drugs were administered acutely at the equianalgesic doses of 0.25 mg/kg for fentanyl and 5 mg/kg for buprenorphine, or delivered continuously with osmotic pumps for 24 h, 3 and 7 days at the rate of 7.5 microg/h per mouse (fentanyl) and 12.5 microg/h per mouse (buprenorphine). After acute administration, a significant decrease of lymphoproliferation is observed in fentanyl-treated animals only. After 24 h of fentanyl administration all the parameters were significantly reduced. After 3 days of fentanyl infusion NK activity had returned to normal values, while all the other parameters were still significantly reduced. In 7 day fentanyl-treated animals immunological tolerance had developed, since no differences with controls were present. In contrast no immune alterations were ever present in buprenorphine-treated animals. No tolerance to the antinociceptive effect of drugs had yet developed. After 1 week of infusion with fentanyl and buprenorphine, new pumps were implanted releasing double amounts of drugs. Neither fentanyl nor buprenorphine-treated animals showed altered immune responses at any time considered. These results indicate that fentanyl and buprenorphine exert different immune effects. Opioid-induced immunosuppression is less relevant in chronic administration than in acute or short-time administration.
Department of Pharmacology, University of Milano, via Vanvitelli 32, 20129 Milano, Italy.
Cataldo
C
Martucci
Alberto E
AE
Panerai
Paola
P
Sacerdote
D000279:Administration, Cutaneous; D000698:Analgesia; D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000276:immunology; D005283:Fentanyl / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D009294:Narcotics / Q000494:pharmacology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
D007376:Interleukin-2; D009294:Narcotics; D003208:Concanavalin A; D002047:Buprenorphine; D007371:Interferon-gamma; D005283:Fentanyl