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REGIONAL ANESTHESIA AND PAIN MANAGEMENT

Pre- Versus Postformalin Effects of Ketamine or Large-Dose Alfentanil in the Rat: Discordance Between Pain Behavior and Spinal Fos-Like Immunoreactivity

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

*Pain Research Clinic, Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland; Department of Psychiatry, McGill University; Pain Mechanisms Research Laboratory, Clinical Research Institute of Montreal; and §Departement de Medecine, Université de Montréal, Montreal, Quebec, Canada

Address correspondence and reprint requests to Ian Gilron, MD, MSc, FRCP(C), Pain Research Clinic, 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

The purpose of this animal investigation was to compare behavioral responses with spinal Fos-like immunoreactivity (FLI) after pre-versus postformalin administration of anesthetic doses of IV ketamine or alfentanil. Preformalin and postformalin injection (1.5% subcutaneously) treatment groups included IV saline control (1.5 mL/kg), ketamine (10 mg/kg), and alfentanil (170 µg/kg). In the behavioral study group, nociceptive behavior was evaluated 15–60 min after hindpaw formalin injection. In the spinal FLI study group, rats were perfused 2 h postformalin, and 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. Ketamine produced a selective preemptive analgesic effect in behavioral formalin experiments, yet failed to suppress spinal FLI. In contrast, alfentanil failed to demonstrate a selective preemptive analgesia in behavioral experiments, but did produce preemptive suppression of spinal FLI. Together with previous data from our laboratory, we conclude that behavioral analgesia and spinal Fos expression may be uncoupled under certain circumstances.

Implications: In this study, we compared pain reduction produced by IV drugs (ketamine or alfentanil) with the ability to prevent injury-induced spinal cord changes. We measured pain behavior and spinal Fos protein after rats received ketamine or alfentanil before versus after formalin injection. Fos inhibition patterns did not clearly correlate with pain reduction, providing further evidence that Fos inhibition is not always predictive of behavioral analgesia.

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