Brain oscillations reflecting pain-related behavior in freely moving rats

Recording oscillatory brain activity holds great promise in pain research. However, experimental results are variable and often difficult to reconcile. Some of these inconsistencies arise from the use of hypothesis-driven analysis approaches that (1) do not assess the consistency of the observed responses within and across individuals, and (2) do not fully exploit information sampled across the entire cortex. Here, we address these issues by recording the electrocorticogram directly from the brain surface of 12 freely moving rats. Using a hypothesis-free approach, we isolated brain oscillations induced by graded nociceptive stimuli and characterized their relation to pain-related behavior. We isolated 4 responses, one phase-locked event-related potential, 2 non-phase-locked event-related synchronizations, and one non-phase-locked event-related desynchronization (ERD), in different frequency bands (delta/theta-ERD, theta/alpha-event-related synchronization, and gamma-band event-related synchronization). All responses except the delta/theta-ERD correlated with pain-related behavior at within-subject level. Notably, the gamma-band event-related synchronization was the only response that reliably correlated with pain-related behavior between subjects. These results comprehensively characterize the physiological properties of the brain oscillations elicited by nociceptive stimuli in freely moving rodents and provide a foundational work to improve the translation of experimental animal findings to human physiology and pathophysiology.