Functional magnetic resonance imaging response to experimental pain in drug-free patients with schizophrenia

https://doi.org/10.1016/j.pscychresns.2010.05.003Get rights and content

Abstract

Clinical evidence suggests that there is decreased pain sensitivity in schizophrenia; however, the neurobiological mechanism of this decrease remains unknown. Using functional magnetic resonance imaging, we examined the blood oxygen level-dependent (BOLD) changes induced by experimental pain-tolerance (endure) hot stimuli vs. non-painful stimuli during an acute psychotic episode in 12 drug-free patients with schizophrenia and in 13 gender- and age-matched healthy controls. The analyses revealed that patients showed a greater BOLD response at S1 compared with controls but a reduced BOLD response in the posterior cingulate cortex (PCC), insula, and brainstem during pain-tolerance stimuli. Pain-tolerance temperature was higher in patients than in healthy controls. BOLD response in the insula positively correlated with unpleasantness and temperature in controls, but this effect was not observed in patients. S1 BOLD response positively correlated with unpleasantness in patients but not in controls. These initial results confirm that unmedicated patients with schizophrenia have a higher pain tolerance than controls, decreased activation in pain affective–cognitive processing regions (insula, PCC, brainstem), and an over-activation of the primary sensory-discriminative pain processing region (S1). These pilot results are the first to explore the mechanism driving altered pain sensitivity in schizophrenia.

Introduction

Schizophrenia is a chronic mental illness characterized by psychotic symptoms, cognitive impairment, apathy and social withdrawal. Among other characteristics of the disease, altered pain sensitivity has been described in patients with schizophrenia since Bleuler and Kraepelin's early observational clinical reports (Bleuler, 1911/1950, Kraepelin, 1919). In addition, the majority of contemporary controlled experimental studies report reduction in pain sensitivity in schizophrenia (Blumensohn et al., 2002, Singh et al., 2006, Potvin et al., 2008).

Neuroimaging studies in healthy controls have mainly implicated the following areas associated with pain anticipation and processing: thalamus, anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), primary (S1) and secondary (S2) somatosensory cortices, insula, dorsolateral prefrontal cortex, ventral striatum, inferior parietal cortex, primary and secondary motor cortices, brainstem, cerebellum, and hippocampus (Gelnar et al., 1999, Davis, 2000, Peyron et al., 2000, Becerra et al., 2001, Pridmore et al., 2003, Apkarian et al., 2005). However, no prior study has examined the brain structures involved during pain processing in schizophrenia. In the present study, we examine the blood oxygen level-dependent (BOLD) changes induced by an experimental pain-tolerance stimulus during an acute psychotic episode in drug-free patients with schizophrenia. Gender- and age-equated healthy controls also completed the functional magnetic resonance imaging (fMRI) protocol with the experimental pain-tolerance stimulus as a comparison group.

Section snippets

Participants

The study was approved by the Ethics and Scientific Committees of the National Institute of Neurology and Neurosurgery of Mexico (NINN), and subjects were included following successful completion of an informed consent procedure.

Seventeen right-handed patients were diagnosed as suffering from schizophrenia on the basis of the Structured Clinical Interview for DSM-IV (First et al., 1997) at the inpatient and outpatient psychiatric services of the NINN from January, 2004 to September, 2006.

Results

The sample included was composed of 12 patients with schizophrenia (10 males) and 13 healthy controls (10 males). There were no differences in gender (χ2 = 0.160, P = 0.68) or age between patients and controls (23.6 ± 3.5 and 26.1 ± 7.2 years, respectively; t = 1.076, df = 23, P = 0.37). The patients' mean age at onset of schizophrenia was 22 ± 3 years with a mean duration of illness of 17 ± 14 months, and a mean PANSS total score of 86.7 ± 19.6 (positive = 20.5 ± 4.6, negative = 22.5 ± 4.9, general = 43.4 ± 10.9) at the time of

Discussion

To our knowledge, this is the first study designed to compare the BOLD response change to experimentally induced pain in drug-free patients with schizophrenia vs. normative data from healthy controls. We found that patients with schizophrenia demonstrated a reduced BOLD response signal in three regions usually recruited in pain processing, specifically the insula, PCC, and brainstem and an increased BOLD response in S1.

The insula, PCC, brainstem (pons and midbrain), and S1 are structures that

Acknowledgments

This work was supported by a National Institute of Neurology and Neurosurgery of Mexico (NINN) internal research support to AG-G and CdlF-S [no. 70/03]; Consejo Nacional de Ciencia y Tecnología (CONACyT) [Pr. 89530 to AG-G]; and Sistema Nacional de Investigadores (SNI) to FP, AG-G and CdlF-S.

We thank Drs. Carlos Campillo, Rogelio Apiquian, Francisco Nente and José Gómez for their assistance in patient recruitment; Drs. Camilo Ríos and Perla Salgado for facilities for the development of this

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