Effects of anesthesia on formalin-induced activation in the forebrain: A neuro-imaging study in rats

We previously reported that formalin-induced pain consistently produces detectable, well-localized, bilateral increases in forebrain activation within multiple somatosensory and limbic structures. The present study investigated the effects of anesthesia with ketamine or isoflurane on forebrain processing during formalin-induced nociception. Accordingly, we measured regional cerebral blood flow to assess brain activation in unanesthetized and anesthetized male Sprague–Dawley (Charles River) rats thirty-five minutes after injection of dilute formalin (2.5%, 0.05 ml, s.c.) into the left hindfoot. We report that both ketamine and isoflurane anesthesia alone (no formalin stimulation) produce robust decreases in brain activation in multiple brain structures, including most cortical and thalamic regions. However, ketamine did produce robust increases in retrospleniel and hippocampal cortices while isoflurane resulted in significant increases in the hypothalamus, habenular complex and the periaqueductal grey. More importantly, the formalin-induced increases in activation within somatosensory and limbic regions normally reported in unanesthetized animals were inhibited by the administration of either ketamine or isoflurane. These data suggest that anesthesia disrupts the activation in regions normally involved in central nociceptive processing while inducing complex changes in brain areas implicated in executive and cognitive functions. These findings have significant implications for the interpretation of in-vivo imaging data from studies using fMRI and microPET in animal models of pain.