Functional magnetic resonance imaging (fMRI) has greatly advanced our current understanding of pain, although most studies to date have focused on imaging of cortical structures. In the present study, we have used fMRI at 3 T to investigate the neural activity evoked by thermal sensation and pain (42 °C and 46 °C) throughout the entire lower neuroaxis from the first synapse in the spinal cord rostral to the thalamus in healthy subjects. The results demonstrate that noxious thermal stimulation (46 °C) produces consistent activity within various structures known to be involved in the pain matrix including the dorsal spinal cord, reticular formation, periaqueductal gray and rostral ventral medulla. However, additional areas of activity were evident that are not considered to be part of the pain matrix, including the olivary nucleus. Thermal stimulation (42 °C) reported as either not painful or mildly painful produced quantitative, but not qualitative, differences in neuronal activity depending on the order of experiments. Activity was greater in the spinal cord and brain stem in earlier experiments, compared with repeated experiments after the more noxious (46 °C) stimulus had been applied. This study provides significant insight into how the lower neuroaxis integrates and responds to pain in humans.

Functional magnetic resonance imaging (fMRI) of the cortex is a powerful tool for neuroscience research, and its use has been extended into the brainstem and spinal cord as well. However, there are significant technical challenges with extrapolating the developments that have been achieved in the cortex to their use in the brainstem and spinal cord. Here, we develop a normalized coordinate system for the cervical spinal cord and brainstem, demonstrating a semiautomated method for spatially normalizing and coregistering fMRI data from these regions. fMRI data from 24 experiments in eight volunteers are normalized and combined to create the first anatomical reference volume, and based on this volume, we define a standardized region-of-interest (ROI) mask, as well as a map of 52 anatomical regions, which can be applied automatically to fMRI results. The normalization is demonstrated to have an accuracy of less than 2 mm in 93% of anatomical test points. The reverse of the normalization procedure is also demonstrated for automatic alignment of the standardized ROI mask and region-label map with fMRI data in its original (unnormalized) format. A reliable method for spatially normalizing fMRI data is essential for analyses of group data and for assessing the effects of spinal cord injury or disease on an individual basis by comparing with results from healthy subjects.