AbstractPain is a complex, multidimensional experience that involves dynamic interactions between sensory-discriminative and affective-emotional processes. Pain experiences have a high degree of variability depending on their context and prior anticipation. Viewing pain perception as a perceptual inference problem, we use a predictive coding paradigm to characterize both evoked and spontaneous pain. We record the local field potentials (LFPs) from the primary somatosensory cortex (S1) and the anterior cingulate cortex (ACC) of freely behaving rats—two regions known to encode the sensory-discriminative and affective-emotional aspects of pain, respectively. We further propose a framework of predictive coding to investigate the temporal coordination of oscillatory activity between the S1 and ACC. Specifically, we develop a high-level, empirical and phenomenological model to describe the macroscopic dynamics of bottom-up and top-down activity. Supported by recent experimental data, we also develop a mechanistic mean-field model to describe the mesoscopic population neuronal dynamics in the S1 and ACC populations, in both naive and chronic pain-treated animals. Our proposed predictive coding models not only replicate important experimental findings, but also provide new mechanistic insight into the uncertainty of expectation, placebo or nocebo effect, and chronic pain.Author SummaryPain perception in the mammalian brain is encoded through multiple brain circuits. The experience of pain is often associated with brain rhythms or neuronal oscillations at different frequencies. Understanding the temporal coordination of neural oscillatory activity from different brain regions is important for dissecting pain circuit mechanisms and revealing differences between distinct pain conditions. Predictive coding is a general computational framework to understand perceptual inference by integrating bottom-up sensory information and top-down expectation. Supported by experimental data, we propose a predictive coding framework for pain perception, and develop empirical and biologically-constrained computational models to characterize oscillatory dynamics of neuronal populations from two cortical circuits—one for the sensory-discriminative experience and the other for affective-emotional experience, and further characterize their temporal coordination under various pain conditions. Our computational study of biologically-constrained neuronal population model reveals important mechanistic insight on pain perception, placebo analgesia, and chronic pain.