Differential encoding of noxious heat and self-reported pain along corticospinal networks: a simultaneous spinal cord-brain fMRI study

Abstract

Chronic pain poses a substantial public health burden. Elucidating how the healthy central nervous system (CNS) differentially encodes objective stimulus intensity and subjective experiences of pain perception may offer key insights into the central mechanisms contributing to chronic pain. Functional MRI (fMRI) combined with controlled noxious stimulation provides a powerful means to explore neural representations of nociception and pain perception. Here, we applied noxious heat at three intensities (46 {degrees}C, 47 {degrees}C, 48 {degrees}C, 8 trials each randomized) to the right forearm of 28 healthy women during simultaneous spinal cord-brain fMRI to investigate how distributed corticospinal activity and connectivity encode stimulus intensity and subjective pain. Activity increased with stimulus temperature across regions involved in pain processing--including somatosensory, motor, prefrontal, insular, and subcortical areas--as well as in the ipsilateral dorsal and ventral spinal cord. Spinal- brain functional connectivity was observed between the right dorsal horn and pain-related brain regions such as primary and secondary somatosensory cortex, insula, anterior cingulate cortex, thalamus, and periaqueductal gray, and was positively associated with individual pain ratings. Using representational similarity analysis (RSA), we found that multivoxel activation patterns in the brain and spinal cord, as well as corticospinal connectivity patterns, reliably tracked stimulus temperature, while only subsets of cortical regions (e.g., insula, sensorimotor, and frontal cortices) encoded subjective pain. Notably, spinal cord representations were primarily organized by stimulus temperature rather than perceived pain intensity. These findings demonstrate that simultaneous spinal cord-brain fMRI combined with multivariate modeling can identify sensory and perceptual components of nociceptive processing across the neuroaxis. Such approaches advance mechanistic understanding of pain and may inform the development of CNS-based biomarkers for chronic pain assessment and intervention.