Background & Aims
Pain is an experience which drives the removal of the individual from actual or potential danger. Nociceptive pathways ascend from the body and head to subcortical and cortical regions, and it has been suggested that nociception from regions of the head evoke more pronounced emotional responses compared to nociception in the body (1). Such differences may dictate differential activation patterns in higher brain regions, specifically in regions processing the affective component of pain (2). Building on our previous work exploring pain activation during acute facial pain we aim to use ultra-high field functional magnetic resonance imaging (fMRI) to determine if painful stimuli applied to the face and body evoke differential activation patterns in awake humans (3,4). We hypothesize that noxious stimulation applied to the face will evoke larger signal changes compared to the body in brainstem, hypothalamic, and subcortical structures that code the affective component of pain.
Methods
Using an MRI-compatible thermode, heat pain was evoked in two orofacial regions (lips and cheek) and two body regions (hand and foot) of 17 healthy participants while they underwent a functional MRI scan (7 tesla MRI; raw voxel size 1x1x1.2mm, repetition time = 2.5 seconds). The stimulation temperature was calibrated to a 5 out of 10 pain rating on a visual analogue scale. During each functional scan, following a 60 second baseline a series of 8 noxious thermal stimuli were applied to one of the four stimulation sites for 15 seconds periods with intervening 15 second baseline periods, repeated 7 times. The thermode was moved to another location and the procedure repeated in each participant. Random effect analysis was performed to confirm cluster activation location with a one-sample t-test (cutoff of p<05, FDR corrected). A participant covariate analysis was included to account for the fact that each subject had two scans in the face, and two scans in the body.
Results
Similar temperature and pain intensity ratings were observed during noxious stimulation on all four sites. Preliminary results from our analysis show larger evoked signal changes and more widespread activation in the face region when compared to body in a number of brain regions. During face stimulation, signal intensity changes occurred in multiple hypothalamic nuclei including within the paraventricular, dorsomedial, ventromedial, arcuate, mamillary body, and posterior hypothalamic nuclei, and in the lateral nucleus of the amygdala. In striking contrast, during noxious stimulation of the body, activation of the hypothalamus was more subdued and limited to the paraventricular and lateral nuclei and no significant activation was observed in the amygdala.
Conclusions
These preliminary results suggest that there may be distinctly different activation patterns during face compared with body pain in areas of the brainstem, hypothalamus, and amygdala. These differential activation patterns may underpin the reported increased affective intensity of face compared with body pain and may play a role in the pathophysiology of chronic pain conditions, particularly those originating in the orofacial region. Further analysis of connectivity between these brain regions may provide additional evidence of a difference between the brain representation of face compared with body pain in humans.
References
1 Schmidt, K. et al. The differential effect of trigeminal vs. peripheral pain stimulation on visual processing and memory encoding is influenced bypain-related fear. Neuroimage 134, 386–395 (2016).
2 Rodriguez, E., Sakurai, K., Xu, J., Chen, Y., Toda, K., Zhao, S., Han, B.X., Ryu, D., Yin, H., Liedtke, W. and Wang, F., 2017. A craniofacial-specific monosynaptic circuit enables heightened affective pain. Nature neuroscience, 20(12), pp.1734-1743.
3 Robertson, R.V., Crawford, L.S., Meylakh, N., Macey, P.M., Macefield, V.G., Keay, K.A. and Henderson, L.A., 2022. Regional hypothalamic, amygdala, and midbrain periaqueductal gray matter recruitment during acute pain in awake humans: A 7-Tesla functional magnetic resonance imaging study. Neuroimage, 259, p.119408.
4 Mendoza, F.A.T., Hughes, T.E., Robertson, R.V., Crawford, L.S., Meylakh, N., Macey, P.M., Macefield, V.G., Keay, K.A. and Henderson, L.A., 2023. Detailed organisation of the human midbrain periaqueductal grey revealed using ultra-high field magnetic resonance imaging. NeuroImage, 266, p.119828.
Presenting Author
Rebecca V Robertson
Poster Authors
Rebecca Robertson
BSc(Hons)
The University of Sydney
Lead Author
Topics
- Pain Imaging