Spinal Cord-Midbrain Functional Connectivity Is Related to Perceived Pain Intensity: A Combined Spino-Cortical fMRI Study

The dynamic interaction between ascending spinocortical nociceptive signaling and the descending control of the dorsal horn (DH) by brain regions such as the periaqueductal gray matter (PAG) plays a critical role in acute and chronic pain. To noninvasively investigate the processing of nociceptive stimuli in humans, previous fMRI studies either focused exclusively on the brain or, more recently, on the spinal cord. However, to relate neuronal responses in the brain to responses in the spinal cord and to assess the functional interplay between both sites in normal and aberrant conditions, fMRI of both regions within one experiment is necessary. Employing a new MRI acquisition protocol with two separate slice stacks, individually adapted resolutions and parameter settings that are dynamically updated to the optimized settings for the respective region we assessed neuronal activity in the spinal cord and in the brain within one measurement at 3 T. Using a parametric pain paradigm with thermal stimulation to the left radial forearm, we observed BOLD responses in the ipsilateral DH of the spinal segment C6 and corresponding neuronal responses in typical pain-processing brain regions. Based on correlations of adjusted time series, we are able to reveal functional connectivity between the spinal C6-DH and the thalamus, primary somatosensory cortex, bilateral insula, bilateral striatum, and key structures of the descending pain-modulatory system such as the PAG, the hypothalamus, and the amygdala. Importantly, the individual strength of the spinal-PAG coupling predicted individual pain ratings highlighting the functional relevance of this system during physiological pain signaling.