Pain perception in schizophrenia: influence of neuropeptides, cognitive disorders, and negative symptoms

Objectives: The causes and nature of insensitivity to pain in schizophrenia remain unknown. The role of endorphins and the association of cognitive dysfunction and negative symptoms are postulated. Methods: In this study, 43 patients with schizophrenia, five first-degree relatives, and 34 healthy controls were examined. Participants' plasma concentrations of substance P,beta-endorphin, and calcitonin gene-related peptide (CGRP) were assessed. In patients, the Trail-Making Test, the Color Reading Interference Test (Stroop test), and the Positive and Negative Syndrome Scale Negative Syndrome subscale (PANSS N) test were performed. We also evaluated pain threshold using nociceptive reflex (RTIII) testing. Results: The mean beta-endorphin concentration was about 20% higher in patients than in healthy controls (P < 0.05). CGRP concentrations were significantly higher in patients than in controls (5.34 ng/mL versus 4.16 ng/mL; P < 0.01). Subjects treated with antipsychotic polytherapy had higher concentrations of CGRP than did patients treated with second-generation antipsychotic monotherapy (5.92 ng/mL versus 5.02 ng/mL; P < 0.05). There were no correlations between any biochemical parameters and Trail-Making Test, Stroop test, and PANSS N scores. There were no differences in RTIII among study groups. Strong negative correlation (P < 0.001) was found between PANSS N scores and subjective pain threshold on the right lower limb. Conclusion: The insensitivity to pain in schizophrenia is a complex phenomenon that is probably not related to changes in nociceptive pathways. Increase in beta-endorphin level may be related to this issue, but it is uncertain if such concentration ensures analgesic effect. It is unknown if patients with schizophrenia in fact experience less pain. Cognitive impairment and excess negative symptoms may strongly influence the patient's expression of pain.