- Autistic adults reported higher subjective pain yet exhibited reduced N2 cortical responses compared with typically developing controls.
- Group by sex interaction: autistic females showed the lowest N2 amplitudes and a weaker link between pain ratings and cortical responses.
- Higher N2 amplitudes correlated with attention-to-detail autistic traits across groups and sexes, suggesting salience or attentional differences in pain processing.
Eur J Pain. 2026 Oct;30(9):e70411. doi: 10.1002/ejp.70411.
ABSTRACT
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.
PMID:42860550 | DOI:10.1002/ejp.70411
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