The dorsal posterior insula subserves a fundamental role in human pain

Abstract

Several brain regions have been implicated in human painful experiences, but none have been proven to be specific to pain. We exploited arterial spin-labeling quantitative perfusion imaging and a newly developed procedure to identify a specific role for the dorsal posterior insula (dpIns) in pain. Tract tracing studies in animals identify a similar region as fundamental to nociception, which suggests the dpIns is its human homolog and, as such, a potential therapeutic target.

Figure 1. Tonic pain ratings over time.

Group mean pain intensity ratings (grey) are plotted over time (x-axis). Error bars represent the standard error of the mean (s.e.m.). Results from the repeat-measures ANOVA are in supplementary table 1.

Figure 2. Whole brain absolute CBF correlation with pain ratings.

a) Contralateral dpIns shows a strong correlation between absolute CBF and pain ratings. Voxels with supra-threshold activation are shown in red (Linear regression; Mixed Effects, z>2.3; p<0.01). Radiological convention is used (L: left; R: right). b) A plot of the group mean tonic pain ratings versus the absolute CBF in the contralateral dpIns. c) Group mean absolute CBF extracted from the peak contralateral dpIns cluster alongside the ongoing pain intensity ratings (grey) over time. Error bars represent the sem. Further analysis of this data set exploring more conventional contrasts of “Peak” period only minus “Baseline” period can be found in Supplementary Information, Supplementary figure 1 and Supplementary table 2.

Figure 3. A schematic of dpIns involvement in human pain studies.

Spherical functional masks were generated from previously reported MNI coordinates linked to the perception of pain. Activation clusters in BLUE and PURPLE represent activation clusters triggered by acute painful stimulation of subjects’ feet using heat (9) or a laser (11). The activation clusters in RED and YELLOW represent surgical coordinates at which direct electrical stimulation resulted in the perception of pain at a particular body site (red = face pain; yellow = lower limb pain) (12). For clarity, the spherical cluster centered at peak zstat reported in the current study is displayed in green. Radiological convention is used (L: left; R: right).