A modality-specific dysfunction of pain processing in schizophrenia

Clinical observations showed that schizophrenia (SCZ) patients reported little or no pain under various conditions that are commonly associated with intense painful sensations, leading to a higher risk of morbidity and mortality. However, this phenomenon has received little attention and its underlying neural mechanisms remain unclear. Here, we conducted two experiments combining psychophysics, electroencephalography (EEG), and functional magnetic resonance imaging (fMRI) techniques to investigate neural mechanisms of pain insensitivity in SCZ patients. Specifically, we adopted a stimulus-response paradigm with brief stimuli of different sensory modalities (i.e., nociceptive, non-nociceptive somatosensory, and auditory) to test whether pain insensitivity in SCZ patients is supra-modal or modality-specific, and used EEG and fMRI techniques to clarify its neural mechanisms. We observed that perceived intensities to nociceptive stimuli were significantly smaller in SCZ patients than healthy controls, whereas perceived intensities to non-nociceptive somatosensory and auditory stimuli were not significantly different. The behavioral results were confirmed by stimulus-evoked brain responses sampled by EEG and fMRI techniques, thus verifying the modality-specific nature of the modulation of nociceptive information processing in SCZ patients. Additionally, significant group differences were observed in the spectral power of alpha oscillations in prestimulus EEG and the seed-based functional connectivity in resting-state fMRI (seeds: the thalamus and periaqueductal gray that are key nodes in ascending and descending pain pathways respectively), suggesting a possible contribution of cortical-subcortical dysfunction to the phenomenon. Overall, our study provides insight into the neural mechanisms of pain insensitivity in SCZ and highlights a need for systematic assessments of their pain-related diseases.