How the Brain Interprets Pain in Autistic People: Does Sex Matter?

BACKGROUND

While psychophysical studies suggest heightened pain sensitivity in individuals with autism spectrum disorder (ASD), the relationship between subjective pain experience and cortical neurophysiological responses and whether this relationship is sex-dependent, remains poorly understood.

METHODS

This cross-sectional two-group comparison study included 50 adults with Level 1 ASD and 52 age-, sex- and IQ-matched typically developing controls (TDC). Pain ratings and cortical contact heat-evoked potentials (CHEPs) were recorded in response to 52°C phasic heat stimuli. ANOVA and regression models assessed the effects of group, sex and pain ratings on CHEP amplitudes.

RESULTS

Compared to TDC, autistic participants reported higher pain scores (p = 0.004) and had lower N2 amplitudes (p = 0.02). A significant Group × Sex interaction (p < 0.001) was associated with the lowest N2 amplitudes in autistic females (p < 0.05). Regardless of group, in females, higher N2 amplitudes were associated with higher pain scores (p = 0.042; model p = 0.032), whereas this association was not significant in males (p > 0.05). Within-group correlation analyses in females showed a significant pain-N2 amplitude relationship in TDC (r = 0.734; p = 0.004) but not in autistic participants (r = 0.371; p = 0.192). Across groups and sexes, higher N2 amplitude values were associated with greater attention-to-detail autistic traits (p = 0.009).

CONCLUSIONS

Our findings suggest a dissociation between subjective pain experience and cortical responses to nociceptive stimulation in autism, particularly among females, consistent with different salience-related or attentional pain processing. These results underscore the importance of considering sex and autism when interpreting pain-evoked cortical responses and challenge the assumption that pain-evoked potentials provide universally objective measures of pain.

SIGNIFICANCE: This study identifies sex-related differences in the relationship between subjective pain ratings and cortical responses to nociceptive stimulation in autistic and typically developing individuals. Autistic females showed particularly attenuated N2 amplitudes and a weaker correspondence between pain ratings and cortical responses, suggesting different salience-related or attentional processing of nociceptive stimuli. These findings highlight the importance of considering sex and autistic traits when interpreting pain-evoked cortical responses in autism.