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Patients With Pain Disorder Show Gray-Matter Loss in Pain-Processing Structures: A Voxel-Based Morphometric Study

From the Neurologische Klinik und Poliklinik (M.V., M.M., T.S., T.R.T.), Klinikum rechts der Isar, Technische Universität München, Germany; Abteilung Psychosomatik und Psychotherapie (H.G.), Medizinische Hochschule Hannover, Germany; Klinik und Poliklinik für Psychiatrie und Psychotherapie (C.S.), Klinikum rechts der Isar, Technische Universität München, Germany; Klinik und Poliklinik für Psychosomatische Medizin (H.G., P.H.), Psychotherapie und Med. Psychologie, Klinikum rechts der Isar, Technische Universität München, Germany; Abteilung für Neuroradiologie (C.Z.), Institut für Röntgendiagnostik, Klinikum rechts der Isar, Technische Universität München, Germany.

Address correspondence and reprint requests to Michael Valet, Neurologische Klinik, Klinikum r.d. Isar der TU München, Ismaninger Str. 22, 81675 München, Germany. E-mail: valet{at}lrz.tum.de

Objective: To investigate whether the functional changes in pain disorder might be reflected by structural brain changes. Pain disorder assessed with the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria is characterized by persistent and distressing chronic pain at one or more body sites which cannot be fully explained by a physiological process or somatic disorder. Psychological factors are thought to play a major role. Recent neuroimaging studies evidenced altered pain processing in patients suffering from this disorder.

Methods: Fourteen right-handed women fulfilling the DSM-IV criteria for pain disorder and 25 healthy age-matched women were investigated with magnetic resonance imaging. In the voxel-based morphometry analysis, we compared both groups for changes of gray-matter density. We included age and Beck Depression Inventory scores as nuisance variables to minimize possible confounding effects of age or depressive comorbidity.

Results: In the patient group, we found significant gray-matter decreases in the prefrontal, cingulate, and insular cortex. These regions are known to be critically involved in the modulation of subjective pain experiences.

Conclusions: In the context of similar results in patients with other functional pain syndromes, such as fibromyalgia and chronic back pain, we suggest that structural changes in fronto-limbic brain circuits represent not only an objective marker of these pain syndromes but also constitute a critical pathophysiological element. These findings represent a further proof of the important role of central changes in pain disorder.

Key Words: pain disorder • idiopathic chronic pain • voxel-based morphometry • orbitofrontal cortex • ventromedial prefrontal cortex • classification

Abbreviations: DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; ICD-10 = International Statistical Classification of Diseases and Related Health Problems, 10th Revision; VBM = voxel-based morphometry; fMRI = functional magnetic resonance imaging; GM = gray matter; WM = white matter; CSF = cerebrospinal fluid; BDI = Beck Depression Inventory; MNI = standardized reference space defined by the Montreal Neurological Institute; SOMS = screening for somatoform symptoms; PPS = Pain Perception Scale; SCID = Structured Clinical Interview for DSM-IV disorders.