A modality‐specific dysfunction of pain processing in schizophrenia

Abstract

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.

Test–retest reliability of laser evoked pain perception and fMRI BOLD responses

“…Hence, assessing the possible effects of psychological state on pain perception and brain responses and monitoring the baseline brain activity are highly needed when designing experiments for laboratory studies and evaluating pain abnormalities in clinical practice. For instance, the across-session variability should be taken into consideration when (1) examining the test-retest reliability of pain perception from multiple experimental sessions; (2) assessing the habituation effect of pain using repeated painful stimulation over several days; and (3) evaluating the long-term analgesic effect of treatment strategies in clinical practice or basic research. Besides, evidence showed that structural MRI features (e.g., gray matter intensity/volume, cortical thickness, subcortical volume) are highly correlated with pain perception in both healthy subjects 38,39 and chronic pain patients [40][41][42] .…”

“…This phenomenon should be considered when designing experiments for laboratory studies and evaluating pain abnormalities in clinical practice.Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) can measure human brain activity objectively and enable a deep understanding of neural processing mechanisms. With this technique, the function of pain pathway structures within the central nervous system in states of acute or chronic pain [1][2][3][4][5][6] , during therapeutic and psychological pain interventions 3,7-9 has been extensively investigated. Recently, accumulating studies suggested that fMRI could be used as a technique to elucidate objective biomarkers for the diagnosis of pain 10,11 as the magnitude of neural responses and self-report pain ratings are highly correlated in many situations 12 .However, pain perception is a very subjective experience, and self-report of pain perception reflects a complex mix of physiological and psychological processes, including nociception, emotion, decision making, selfawareness, social cognition, and communicative tendencies 13 .…”

Pain Sensitivity in Schizophrenia Spectrum Disorders: A Narrative Review of Recent Work

“…By contrast, some studies have reported hypersensitivity to pain in schizophrenia [13]. This may depend on the character of the pain stimulus [15]. The differentiation of acute from chronic pain is also important.…”

“…It seemed more likely that cognitive impairment and the presence of negative symptoms were decreasing the expression of pain. Nevertheless, a recent study investigating neural mechanisms of pain sensitivity in patients with schizophrenia by means of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) [15] found that schizophrenia patients showed a lower perceived intensity to nociceptive stimuli compared to healthy controls but similar perceived intensity to non-nociceptive somatosensory and auditory stimuli. This suggests that schizophrenia patients respond differently to pain than to other stimuli.…”

Differential Physical and Mental Benefits of Physiotherapy Program Among Patients With Schizophrenia and Healthy Controls Suggesting Different Physical Characteristics and Needs

“…The unexpected finding of increased pain perception in patients with SCZ deserves special considerations, since recent studies demonstrated that patients with SCZ ( 31 – 33 ) have a higher pain threshold for pain than the general population and lower measures of pain than do other patients with major psychiatric disorders, particularly bipolar disorder. As expected ( 34 ), patients in early stages of illness had more pain than those with more advanced stages and HC.…”