Functional Magnetic Resonance Imaging of Pain in the Spinal Cord and Brainstem

Abstract

Functional magnetic resonance imaging (fMRI) studies performed to date have focused on brain structures rostral to the thalamus, although the first level of sensory information and pain transmission occurs at the spinal cord (SC). The primary goal of this project is to map activity using fMRI, from the entire cervical SC and brainstem following innocuous and noxious stimuli before and after peripheral sensitization in normal human volunteers. This study is unique in that it determines functional activity throughout the lower neural axis in response to mechanical stimuli that are perceived as painful only after sensitization.

Functional MRI studies of the SC were carried out in 18 healthy individuals in a 3T Siemens Magnetom Trio. Innocuous touch and brush (n=8), and noxious touch (n=10) stimuli were applied before and after peripheral sensitization. Peripheral sensitization was induced by topical application of capsaicin. Functional image data spanned from the C7/T1 disc to the superior edge of the thalamus and analyzed using a general linear model to discriminate signal intensity changes from physiological motion. Normalized results were combined to demonstrate the number of volunteers showing activity at each location on a voxel-by-voxel basis. Areas of activity were superimposed onto anatomical transverse drawings and identified visually with comparison to several stereotaxic atlases.

The results from this study confirm previous reports that a non-noxious stimulus translates into a pain response after peripheral sensitization. The brush stimulus, before sensitization activated areas in the ipsilateral dorsal horn (DH), gracile and cuneate nuclei in the medulla and areas surrounding the dorsal column medial lemniscal pathway. Peripheral sensitization produced activity in the contralateral ventral horn (VH), typical of a pain response. The innocuous von Frey stimulus produced activity in typical sensory centres in the DH and brainstem before sensitization, and areas more consistent with a noxious response after sensitization. When examining equi-nociceptive stimuli in a control versus sensitized state, the noxious touch stimuli showed similar activation patterns even though the force of the filaments were different. In all experiments there was indication of descending modulation as activity was observed in the periaqueductal gray, midbrain red nuclei and pontine reticular formation. This study demonstrates how non-painful and pain information is transmitted from the dorsal spinal horn to the brain in healthy individuals and how peripheral sensitization induces changes in non-noxious stimuli that correlate with pain sensory transmission.