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ANALGESIA

Suppression of Noxious-Induced C-Fos Expression in the Rat Lumbar Spinal Cord by Isoflurane Alone or Combined with Fentanyl

Mathieu G. Sommers, DVM^*, Nha-Khanh Nguyen, MSc, Jan G. Veening, PhD, Kris C. Vissers, MD, PhD, FIPP, Merel Ritskes-Hoitinga, DVM, PhD, Dipl ECLAM^*, and Jan van Egmond, PhD

From the *Central Animal Laboratory, Department of Anatomy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Department of Psychopharmacology, UIPS, Utrecht University, Utrecht, The Netherlands; and Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Address correspondence and reprint requests to Mathieu G. Sommers, DVM, P.O. Box 9101, 231 CDL, NL-6500 HB Nijmegen, The Netherlands. Address e-mail to M.Sommers{at}cdl.umcn.nl.

Abstract

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 minimum alveolar concentration (MAC) isoflurane anesthesia groups (unstimulated/NIWR-stimulated) and two NIWR-stimulated surgical anesthesia groups (1 MAC isoflurane anesthesia and MAC isoflurane anesthesia combined with fentanyl 400–600 µg · kg^–1 · 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.

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