Electroencephalographic responses to the formalin test in rats

Abstract

The formalin test is an animal model of persistent pain. Although biphasic behavioral responses to formalin injection have been well described, the significance of the biphasic time course of the pain behaviors has not been established. To explore the significance of the behavioral responses to the formalin injection, we measured and analyzed cortical electroencephalogram (EEG) during the formalin tests in rats. Formalin was injected subcutaneously in the hindpaw of freely moving rats, and behavioral responses were visually counted and recorded. Results were compared with a control group which received saline injection. Neocortical EEG was recorded from implanted dural surface electrodes and analyzed using a Fast Fourier Transformation. Formalin produced biphasic pain behaviors with a transient pause between two phases. Cortical EEG recordings showed a biphasic change; a vigilant pattern (a low amplitude high frequency activity) followed by a non-vigilant pattern (a high amplitude low frequency activity), showing a good correlation with apparent arousal states of rats. Observed discrepancies between pain behaviors and EEG-measured vigilance stages included (1) a vigilant EEG pattern persisted during the transient pause of pain behavior, and (2) pain behaviors persisted even after non-vigilant EEG pattern became dominant. The results of the current study showed that there are temporal discrepancies between the pain behaviors and EEG-measured vigilance during the formalin test in rats. The temporal relationship between the 'pain' behaviors and nociception per se may not be as solid as believed.