Differential brain activation associated with laser-evoked burning and pricking pain: An event-related fMRI study

Abstract

An important question remains as to how the brain differentially processes first (pricking) pain mediated by Adelta-nociceptors versus second (burning) pain mediated by C-nociceptors. In the present cross-over randomized, within-subjects controlled study, brain activity patterns were examined with event-related fMRI while pricking and burning pain were selectively evoked using a diode laser. Stimuli evoking equivalent pain intensities were delivered to the dorsum of the left foot. Different laser parameters were used to elicit pricking (60ms pulse duration) and burning (2.0s pulse duration) pain. Whole brain group analysis showed that several brain areas were commonly activated by pricking and burning pain, including bilateral thalamus, bilateral anterior insula, bilateral posterior parietal lobule, contralateral dorsolateral prefrontal cortex, ipsilateral cerebellum, and mid anterior cingulate cortex. These findings show that pricking and burning pain were associated with activity in many of the same nociceptive processing brain regions. This may be expected given that Adelta-and C-nociceptive signals converge to a great extent at the level of the dorsal horn. Other brain regions showed differential processing. Stronger activation in the pricking pain condition was found in the ipsilateral hippocampus, bilateral parahippocampal gyrus, bilateral fusiform gyrus, contralateral cerebellum and contralateral cuneus/parieto-occipital sulcus. Stronger activation in the burning pain condition was found in the ipsilateral dorsolateral prefrontal cortex. These differential activation patterns suggest preferential importance of Adelta-fiber signals versus C-fiber signals for these specific brain regions.

Figures

Figure 1.

Pain intensity and pain unpleasantness ratings. The boxplots presented on the left side of the figure represent pain intensity ratings for each session and pain stimulation separately. Additionally, individual scores for each subject are presented as open dots in the box plots. A, mean pain intensity rating over 10 trials as determined in the screening session for the burning and pricking conditions separately. B, average pain intensity rating over a block of 30 trials in the MRI session for the burning and pricking conditions separately. No significant differences in pain intensity ratings were found between conditions of burning and pricking pain in the screening session or the MRI session. The boxplots presented on the right side of the figure represent pain unpleasantness ratings for each session and pain stimulation separately. A, average pain unpleasantness rating over 10 trials in the screening session. B, average unpleasantness rating over a block of 30 trials in the MRI session. Also, no significant differences in pain unpleasantness ratings were found between conditions of burning and pricking pain in the screening session or the MRI session.

Figure 2.

Time course of brain activation following pricking and burning pain. Time course of BOLD signal change in selected ROIs following laser stimulation in the (A) pricking pain and (B) burning pain conditions. Stimulation onset was at 0 seconds. The right side of the brain is contralateral to stimulation. Error bars represent standard errors.

Figure 2.

Time course of brain activation following pricking and burning pain. Time course of BOLD signal change in selected ROIs following laser stimulation in the (A) pricking pain and (B) burning pain conditions. Stimulation onset was at 0 seconds. The right side of the brain is contralateral to stimulation. Error bars represent standard errors.

Figure 3.

Activation and overlap maps. Activation maps for the pricking (column 1) and burning (column 2) pain conditions separately, and the overlap map of activation between these conditions (column 3; superimposition of the two activation maps). The left side of each image corresponds to the right side of the brain, which is contralateral to stimulation. Functional activation maps are overlaid on a normalized anatomical MRI in Talairach space. The coordinates of slice cuts through the axial and sagittal planes are presented in the images. The color bar represents the extent of activation in z-scores of the pricking and burning pain activation maps. The minimum cluster size threshold in the group overlap analysis was 4 voxels in original space at an overall p

Figure 4.

Contrast maps. Brain regions differentially activated by the burning and pricking pain stimulation. The left side of each image corresponds to the right side of the brain, which is contralateral to stimulation. Functional run activation is overlaid on a normalized anatomical MRI in Talairach space. The coordinates of slice cuts through the axial and coronal planes are presented in the images. Orange regions represent stronger activation in the pricking versus burning condition, while blue areas represent stronger activation in the burning versus pricking condition. In the group contrast analysis, the minimum cluster size was 6 voxels in original space at an overall p