Nonlinear Relationship between Perception of Deep Pain and Medial Prefrontal Cortex Response Is Related to Sympathovagal Balance

Brain responses to evoked pain have been extensively investigated during the past years. Medial prefrontal cortex (MPFC) has been identified as a region showing a nonlinear, quadratic response to increasing evoked deep pain. Concurrently, MPFC plays an important role as an autonomic mediator in pain perception. Therefore, we hypothesize that MPFC response to pain is directly correlated with autonomic outflow. In order to test our hypothesis, we integrated autonomic modulation with functional neuroimaging data (BOLD fMRI) obtained during evoked deep tissue pain. We selected the LF/HF ratio, estimated instantaneously through a point process approach, as a measure of sympathovagal balance. Our findings reveal that mean LF/HF values show a nonlinear, U-shaped response to increasing pain, supporting our initial hypothesis. Furthermore, we found that subjects with higher LF/HF ratios, that is, higher shift towards sympathetic outflow, also show increased activation in the ventral portion of MPFC, thus providing further evidence in support of the relevant role of this region in sympathetic modulation.