Suppression of noxious-induced c-fos expression in the rat lumbar spinal cord by isoflurane alone or combined with fentanyl.
BACKGROUND
Although our understanding of nociceptive processing during anesthesia has increased greatly over the last decade, many patients still experience hyperalgesia and acute pain postoperatively. The noxious-induced withdrawal reflex (NIWR) model is specifically designed and validated to quantitatively study the reaction on painful, multimodal stimuli in animals under anesthetic conditions. Since the anesthetic mechanisms differ between inhaled anesthetics and opioids, we evaluated the differential effects of isoflurane and fentanyl on c-fos expression at the lumbar level as a measure of nociceptive information transfer during general anesthesia.


METHODS
The experimental setup consisted of a randomized block design with four experimental groups: two light (3/4) minimum alveolar concentration (MAC) isoflurane anesthesia groups (unstimulated/NIWR-stimulated) and two NIWR-stimulated surgical anesthesia groups (1(1/2) MAC isoflurane anesthesia and (3/4) MAC isoflurane anesthesia combined with fentanyl 400-600 microg x kg(-1) x h(-1)). After 2 h of intermittent electrical stimulation of the hind paw of the rat, the number of Fos immunoreactive (Fos-IR) neurons in the dorsal horn was measured quantitatively.


RESULTS
The main suppressive effects on lumbar c-fos expression of isoflurane were observed in the superficial lamina II (P = 0.02), whereas fentanyl showed the strongest effects in lamina V (P = 0.05).


CONCLUSIONS
This study demonstrates that the NIWR model combined with spinal Fos-immunoreactivity is a suitable and useful model for evaluating the differential effects of inhaled anesthetics and opioids on nociceptive information transfer during general anesthesia.
Sommers
Mathieu G
MG
Central Animal Laboratory, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. M.Sommers@cdl.umcn.nl
Nguyen
Nha-Khanh
NK
Veening
Jan G
JG
Vissers
Kris C
KC
Ritskes-Hoitinga
Merel
M
van Egmond
Jan
J
D000700:Analgesics / Q000627:therapeutic use; D000758:Anesthesia; D000818:Animals; D004359:Drug Therapy, Combination; D004558:Electric Stimulation; D005283:Fentanyl / Q000627:therapeutic use*; D007530:Isoflurane / Q000627:therapeutic use*; D008159:Lumbar Vertebrae; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D016760:Proto-Oncogene Proteins c-fos; D007530:Isoflurane; D005283:Fentanyl