Morphine reduces spinal c-fos expression dose-dependently during experimental laparotomy in pigs: a combined pharmacokinetic and surgical study.
The pharmacokinetics of intravenous morphine 2.5mg/kg (n=4) and 10mg/kg (n=4) in plasma and cerebrospinal fluid (CSF) of pigs was studied. Plasma half-life was 1.0+/-0.1h and the main metabolite was morphine-3-glucuronide, whereas morphine-6-glucuronide was negligible. CSF morphine concentration peaked after 20-30min (2.5mg/kg) and 60-120min (10mg/kg), and elimination half-life was 3.5+/-0.3h. Subsequently, the effect of morphine on surgery-induced spinal nociception in pigs subjected to unilateral laparotomy was evaluated by stereological quantification of the total number of Fos-like-immunoreactive (Fos-LI) spinal neurons of the dorsal horn. Surgery (n=4) induced 91,680+/-14,974 Fos-LI neurons ipsilaterally and morphine reduced this number to 45,771+/-8755 following the 2.5mg/kg dose (p<0.01; n=6) and 14,981+/-2327 following the 10mg/kg dose (p<0.001; n=6). These results indicate that morphine dose-dependently reduces the number of surgery-induced Fos-LI neurons in the spinal cord. As even a high dose of morphine does not reduce spinal c-fos expression to basal level, it may be appropriate to use other analgesics simultaneously with morphine during surgery.
Department of Pharmacology and Pathobiology, The Royal Veterinary and Agricultural University, 9 Ridebanevej, DK-1870 Frederiksberg C, Copenhagen, Denmark. kl@rheoscience.com
K
K
Lykkegaard
J
J
Lykkesfeldt
B
B
Lauritzen
O
O
Svendsen
D000818:Animals; D001835:Body Weight; D005260:Female; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D007813:Laparotomy / Q000379:methods / Q000662:veterinary*; D009020:Morphine / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013552:Swine
D009020:Morphine