Article Text

  1. D. Ludlow,
  2. D. Soneji,
  3. T. Ueno,
  4. G. Glover,
  5. S. Mackey
  1. Stanford University; Stanford, CA


Introduction Chronic pain has a tremendous impact on individual patients, their families, and society. Functional magnetic resonance imaging (fMRI) has been used to investigate nociceptive processing and central sensitization in the brain to better understand and to ultimately develop improved therapies for chronic pain. The spinal cord is important in the processing of nociception, and direct animal and indirect psychophysical and behavioral human studies have demonstrated its role in the generation and maintenance of hyperalgesia and allodynia. The goal of this study was to use fMRI to investigate nociceptive processing within the human spinal cord. Our hypothesis was that increases in noxious thermal stimuli will produce a corresponding increase in fMRI signal activation in the human spinal dorsal horn and increases in spatial and rostrocaudal activity.

Methods Following IRB approval, 10 healthy adults were recruited. Subjects were tested prior to scanning to assess tolerability to 12 repetitive 30 sec blocks of 46°C, 47°C, and 48°C thermal stimuli applied to the distal lateral forearm using a computer-controlled Peltier thermode. Subjects were then scanned in a 3T GE MRI system using a custom-built cervical spine surface coil. Functional scans were collected in each subject from the top of C5 through the bottom of C7. Stimuli were delivered in an identical fashion to the prescanning session. Functional images were retrospectively corrected to reduce noise created by the respiratory cycle and cardiac pulsatility. The data were then analyzed to measure both voxel significance and percent blood oxygen level-dependent (BOLD) changes.

Results Spinal fMRI activity to noxious stimuli was well localized to the ipsilateral superficial and deep dorsal horn at the spinal cord level corresponding to the dermatomal region stimulated. There was an increasing fMRI BOLD signal in the dorsal horn associated with increasing magnitude of thermal stimuli. Additionally, with increasing thermal stimuli there were both increases in rostrocaudal extension of dorsal horn activity as well as increases in contralateral dorsal horn activity.

Conclusions These results support our hypothesis and suggest that both population coding and changes in individual voxel activation in the spinal cord play a role in encoding pain intensity in humans. This is consistent with animal models of spinal cord nociceptive processing. These data can be used to investigate further central changes that may play a role in acute and chronic pain and may provide a more objective means of assessing nerve function in patients with peripheral nerve and spinal cord injury.

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