Pain anticipation: an activation likelihood estimation meta-analysis of brain imaging studies

Abstract

The anticipation of pain has been investigated in a variety of brain imaging studies. Importantly, today there is no clear overall picture of the areas that are involved in different studies and the exact role of these regions in pain expectation remains especially unexploited. To address this issue, we used activation likelihood estimation meta-analysis to analyze pain anticipation in several neuroimaging studies. A total of 19 functional magnetic resonance imaging were included in the analysis to search for the cortical areas involved in pain anticipation in human experimental models. During anticipation, activated foci were found in the dorsolateral prefrontal, midcingulate and anterior insula cortices, medial and inferior frontal gyri, inferior parietal lobule, middle and superior temporal gyrus, thalamus, and caudate. Deactivated foci were found in the anterior cingulate, superior frontal gyrus, parahippocampal gyrus and in the claustrum. The results of the meta-analytic connectivity analysis provide an overall view of the brain responses triggered by the anticipation of a noxious stimulus. Such a highly distributed perceptual set of self-regulation may prime brain regions to process information where emotion, action and perception as well as their related subcategories play a central role. Not only do these findings provide important information on the neural events when anticipating pain, but also they may give a perspective into nocebo responses, whereby negative expectations may lead to pain worsening.

Keywords: activation likelihood estimation meta-analysis; anterior cingulate cortex; anterior insula; expectation; functional magnetic resonance imaging; meta-analytic connectivity model; pain anticipation.

Figure 1

PRISMA (2009) Flow Diagram of article selection.

Figure 2

Upper Panel: ALE maps were computed using GingerALE 2.3.1 at an FDR‐corrected threshold of P < 0.05, with a minimum cluster size of K > 50 mm³ and visualized using MRIcron. Lower Panel: Activations and deactivations were projected onto a 3D rendering model of the brain.

Figure 3

Upper Panel: Meta‐analytic connectivity modeling (MACM) assessment of anterior insula (A) and cingulate (B) corteces functional connectivity. MACM maps were computed using Lower Panel: Functional characterization by behavioural domain. The red/blue bars denote the number of foci for the particular behavioural domain within the AI and ACC selected ROI.