Cortical 6-9 Hz Oscillation are a Reliable Biomarker of Persistent Pain in Rats

Neural biomarkers of chronic pain offer a potential tool for improving the speed of diagnosis and delivery of treatment for this devastating disease. Here, we tested the hypothesis that pain states are associated with distinct changed in cortical brain waves. We induced neuropathic orofacial pain in female rats by chronic constriction injury of the infraorbital nerve (CCI-ION). In most animals, this resulted in lasting reductions in mechanical sensitivity thresholds, and in lasting increases in facial grimace scores. We recorded electrocortigraphy (ECoG) signals over the neocortex of these rats, before and after CCI-ION, and analyzed these signals with a novel, spectral modelling approach. Consistent with our hypothesis, power in the 6-9 Hz bandwidth of the ECoG was differentially modulated in animals displaying signs of chronic pain. Specifically, development of mechanical hypersensitivity correlated with a decrease in 6-9 Hz power. Furthermore, we show that changes in the power of this oscillation after injury, obtained at the individual animal level, provide a more sensitive marker of pain presence than do traditional between animal comparisons of post-injury oscillatory power. Identification of animals demonstrating chronic-pain behaviors was more accurate when estimates of post-injury oscillatory power were compared against each animals own pre-injury baseline than when compared against post-injury power estimates from animals not developing chronic pain. These results highlight the need for establishing individual-specific, "pain-free" baselines from which oscillation disturbances can be measured and which may constitute a reliable, low-cost approach not only for diagnosing chronic pain, but also for identifying individuals likely to transition from acute to chronic pain.