A Comparison of Functional Connectivity in the Human Brainstem and Spinal Cord Associated with Noxious and Innocuous Thermal Stimulation Identified by Means of Functional MRI

Abstract

The somatosensory system is multidimensional and processes important information for survival, including the experience of pain. The brainstem and spinal cord serve pivotal roles in both transmitting and modulating pain signals from the periphery; although, they are studied less frequently with neuroimaging when compared to the brain. In addition, imaging studies of pain often lack a sensory control condition, failing to differentiate the neural processes associated with pain versus innocuous sensations. The purpose of this study was to investigate neural connectivity between key regions involved in descending modulation of pain in response to a hot, noxious stimulus as compared to a warm, innocuous stimulus. This was achieved with functional magnetic resonance imaging (fMRI) of the brainstem and spinal cord in 20 healthy men and women. Functional connectivity was observed to vary between specific regions across painful and innocuous conditions. However, the same variations were not observed in the period of anticipation prior to the onset of stimulation. Specific connections varied with individual pain scores only during the noxious stimulation condition, indicating a significant role of individual differences in the experience of pain which are distinct from that of innocuous sensation. The results also illustrate significant differences in descending modulation before and during stimulation in both conditions. These findings contribute to a deeper understanding of the mechanisms underlying pain processing at the level of the brainstem and spinal cord, and how pain is modulated.

Recent developments and future avenues for human corticospinal neuroimaging

“…While many studies exist exploring bidirectional pain processing and modulation along the spinal-brainstem circuitry ( Ghazni et al, 2010 ; Cahill and Stroman, 2011 ; Bosma et al, 2015 ; Rempe et al, 2015 ; Stroman et al, 2016 , 2018 ; Sprenger et al, 2018 ; Yessick et al, 2021 ; Ioachim et al, 2022 ; Koning et al, 2023 ), only a handful included supraspinal cortical regions to explore sensory ( Sprenger et al, 2015 , 2018 ; Tinnermann et al, 2017 ; Oliva et al, 2022 ) or motor ( Vahdat et al, 2015 ; Islam et al, 2019 ; Khatibi et al, 2022 ; Braass et al, 2023 ) information flow along the neuroaxis. Methodological developments intended to overcome challenges in image acquisition and data processing are recently evolving ( Cohen-Adad et al, 2010 ; Finsterbusch et al, 2013 ; Islam et al, 2019 ; Finsterbusch and Chu, 2023 ).…”

“…Corticospinal fMRI enables investigating temporal associations of activated regions along the CNS. Increased experimental pain-induced activity in the spinal dorsal horn (dermatome C6) and brainstem areas could be reproduced using the combined imaging approach in healthy participants ( Ghazni et al, 2010 ; Cahill and Stroman, 2011 ; Bosma et al, 2015 ; Rempe et al, 2015 ; Sprenger et al, 2018 ; Stroman et al, 2018 ; Koning et al, 2023 ). Furthermore, it could be extended to observations of pathologically altered activation and spinal cord-brainstem connectivity related to pain modulation in spinal cord injury ( Stroman et al, 2016 ), fibromyalgia ( Ioachim et al, 2022 ), and women with provoked vestibulodynia ( Yessick et al, 2021 ).…”

“…Furthermore, it could be extended to observations of pathologically altered activation and spinal cord-brainstem connectivity related to pain modulation in spinal cord injury ( Stroman et al, 2016 ), fibromyalgia ( Ioachim et al, 2022 ), and women with provoked vestibulodynia ( Yessick et al, 2021 ). Interestingly, the degree of interaction between spinal circuitries (at the stimulation level) and the PAG (as measured by functional connectivity) during painful heat stimulation was associated with pain intensity ratings of healthy volunteers ( Sprenger et al, 2015 ; Koning et al, 2023 ). The descending pain-inhibitory connection between the brainstem and spinal networks was further reportedly changed during cognitive/emotional regulation (i.e., inhibition) ( Stroman et al, 2011 ; Oliva et al, 2022 ) and secondary hyperalgesia (i.e., disinhibition) ( Rempe et al, 2014 ) in healthy participants.…”

The psychophysiology of music-based interventions and the experience of pain

“…The spinal cord is a major site of nociceptive modulation, involving many neuroactive agents and mediated by complex synaptic interactions between afferent sensory inputs and descending and local excitatory and inhibitory circuits. The functional output from this milieu is further complicated by altered activity and signaling across pain conditions, and by individual differences in response profiles (e.g., D' Mello and Dickenson, 2008;Heijmans et al, 2021;Koning et al, 2023). Recent studies also implicate astrocytes in modulatory mechanisms within spinal cord (Chen Y. L. et al, 2022;Chen W. G. et al, 2022).…”