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REGIONAL ANESTHESIA AND PAIN MANAGEMENT

Pre- Versus Postinjury Effects of Intravenous GABAergic Anesthetics on Formalin-Induced Fos Immunoreactivity in the Rat Spinal Cord

Ian Gilron, MD, MSc, FRCP(C)^*, Rémi Quirion, PhD, and Terence J. Coderre, PhD^,,||

*National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland; Douglas Hospital Research Centre, Verdun, Québec, Canada and Department of Psychology, McGill University; Pain Mechanisms Research Laboratory, Clinical Research Institute of Montréal; and ||Département de Médecine, Université de Montréal, Montreal, Quebec, Canada

Address correspondence and reprint requests to Ian Gilron, MD, MSc, FRCP(C), Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 10, Room 3C-434, 9000 Rockville Pike, Bethesda, MD 20892. Address e-mail to igilron{at}yoda.nidr.nih.gov

We evaluated the suppression of spinal Fos-like immunoreactivity (FLI) by IV anesthetics in the rat formalin model. Preformalin injection (1.5% subcutaneously) treatment groups included IV saline controls and three IV GABAergic anesthetic groups (pentobarbital 20 mg/kg, propofol 10 mg/kg, or alphaxalone 1.5 mg/kg; n = 12 per group). After perfusion 2 h postformalin, spinal cords were dissected, sliced at 30 µm, and processed by immunoperoxidase staining with an antibody against the Fos protein. Quantification and determination of the laminar distribution of Fos-labeled nuclei were performed at the L4-5 spinal level ipsilateral to formalin injection. Drug groups demonstrating FLI suppression were comparatively studied in a 5-min postformalin treatment group. Pentobarbital pretreatment failed to suppress FLI. However, significant reductions (percent decrease) of FLI were observed with propofol (63%) and alphaxalone (30%) compared with saline controls. Pre- versus postformalin comparison studies showed that propofol, but not alphaxalone, suppressed FLI more effectively when given preformalin. Given the observed inconsistencies between this study of Fos expression and our previous behavioral study, it is questionable whether anesthetic modulation of noxious stimulus-induced FLI parallels that of behavioral responses.

Implications: In this study, we examined whether IV general anesthetics (propofol, alphaxalone, and pentobarbital) prevent injury-induced spinal cord changes. We measured spinal Fos protein after rats received anesthetics before versus after a formalin injection. Fos inhibition patterns were inconsistent with behavioral studies of these anesthetics, suggesting that Fos inhibition does not always correlate with behavioral analgesia.

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