Figure 1.

Wheel within a wheel: the epic pain model. Schematic representation of functional connectivity between the major sensory pathway (thalamus and somatosensory granular cortex), and agranular cortical areas which are continuously engaged in generating internal predictions based on interoceptive inference, even in the absence of external sensory input. The farther away an external sensory stimulus falls from the internal prediction (i.e., a powerfully salient, unexpected or “unexplained” painful event), the larger the prediction “error signal.” The objective of this feedback-feedforward dialog (which we refer to as the epic pain model) is to coordinate optimal cortical responses along two putative functional connectivity patterns: thalamic bursts via TRN, and bidirectional communication between agranular cortex (limbic/paralimbic) and granular cortex (somatosensory). According to this model, the error signal is rectified when internal predictions are updated with new information about the environment or, in the case of chronic pain, when cortical mechanisms lead to successful coping behaviors.