Temporally Distinct Neural Responses to Pain in ASD: Evidence for Altered Cognitive Pain Modulation and Relationships to Self-Injurious Behaviors

Background:   There is a prevalent assumption that individuals with autism spectrum disorders (ASD) are less sensitive to pain. Yet, this assertion is not well supported by empirical evidence. Importantly, communication deficits make assessing pain through verbal reports particularly challenging in ASD. Objective markers of pain, such as neural responses obtained with neuroimaging, have been suggested as a means of clarifying the pain experience in vulnerable populations. Previous work has identified a neural pain signature (somatosensory cortices, insula, anterior cingulate) using functional magnetic resonance imaging (fMRI) that differentiates pain from innocuous stimulation. 

Objectives:   The goal of this study was to determine whether the temporal or spatial properties of the neural pain signature differ in individuals with ASD, and if so, what possible modulators outside the identified neural pain signature contribute to these differences. We also sought to explore whether differences in the signature relate to self-injurious behaviors that are thought to arise from aberrant pain processing in ASD.

Methods:  Participants included 16 adults with ASD and 16 adults without ASD in a typical comparison group. Self-injurious behaviors were assessed with the Repetitive Behavior Scale-Revised; participants with ASD were categorized by presence or absence of self-injurious behaviors. Neural response to sustained heat pain was assessed with fMRI using a block design. For each trial, heat was applied to the right lateral calf for 21 seconds (15 seconds at target temperature, 3 second ramp up/down) followed by 39 seconds rest period.

Results:  The two groups had similar pain ratings and pain thresholds, in addition to similar neural pain signature responses during acute pain. Yet, there was a highly exaggerated suppression of the neural pain signature in ASD during intermediate and late phases of sustained pain (Z>2.3, p<0.001, corrected). Direct group contrasts revealed greater response in the typical comparison group compared to ASD in dorsolateral prefrontal cortex and posterior cingulate regions during intermediate and late phases. Additionally, this widespread, late suppression of the neural pain signature in ASD was more prominent in the subgroup of individuals with self-injurious behaviors.

Conclusions:  Late suppression of the neural pain signature may indicate aberrant pain processing in ASD associated with self-injurious behavior. Altered activity in areas thought to modulate the pain experience (dorsolateral prefrontal cortex and posterior cingulate) suggests a wider potential selection of coping strategies available to the typical comparison group than the ASD group during sustained pain. The contrast between equivalent pain ratings and striking differences in the neural pain response suggests individuals with ASD may have an altered experience of pain that is not reflected in their subjective pain ratings. Future studies will need examine functional connectivity within the neural pain signature in ASD and in connection with modulating regions in order to understand the mechanism of this altered processing.