Changes in brain function and morphology in patients with recurring herpes simplex virus infections and chronic pain

Vartiainen, Nuutti; Kallio-Laine, Katariina; Hlushchuk, Yevhen; Kirveskari, Erika; Seppänen, Mikko; Autti, Henri; Jousmäki, Veikko; Forss, Nina; Kalso, Eija; Hari, Riitta

doi:10.1016/j.pain.2009.04.015

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Volume 144, Issue 1 , Pages 200-208, July 2009

Changes in brain function and morphology in patients with recurring herpes simplex virus infections and chronic pain

Nuutti Vartiainen
- Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, FI-02015 TKK, Espoo, Finland
- Advanced Magnetic Imaging Centre, Helsinki University of Technology, FI-02015 TKK, Espoo, Finland
- Corresponding author. Address: Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, P.O. Box 5100 FI-02015 TKK, Espoo, Finland. Tel.: +358 9 4512953; fax: +358 94513508.
- These authors contributed equally to the study.
Katariina Kallio-Laine
- Department of Anesthesiology and Intensive Care Medicine, Pain Clinic, Helsinki University Central Hospital, FI-00029 HUS, Helsinki, Finland
- These authors contributed equally to the study.
Yevhen Hlushchuk
- Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, FI-02015 TKK, Espoo, Finland
- Advanced Magnetic Imaging Centre, Helsinki University of Technology, FI-02015 TKK, Espoo, Finland
Erika Kirveskari
- Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, FI-02015 TKK, Espoo, Finland
- Department of Clinical Neurophysiology, Helsinki University Central Hospital, FI-00029 HUS, Helsinki, Finland
Mikko Seppänen
- Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, FI-00029 HUS, Helsinki, Finland
Henri Autti
- Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, FI-02015 TKK, Espoo, Finland
- Advanced Magnetic Imaging Centre, Helsinki University of Technology, FI-02015 TKK, Espoo, Finland
Veikko Jousmäki
- Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, FI-02015 TKK, Espoo, Finland
- Advanced Magnetic Imaging Centre, Helsinki University of Technology, FI-02015 TKK, Espoo, Finland
Nina Forss
- Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, FI-02015 TKK, Espoo, Finland
- Department of Clinical Neurosciences, Helsinki University Central Hospital, FI-00029 HUS, Helsinki, Finland
Eija Kalso
- Department of Anesthesiology and Intensive Care Medicine, Pain Clinic, Helsinki University Central Hospital, FI-00029 HUS, Helsinki, Finland
Riitta Hari
- Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, FI-02015 TKK, Espoo, Finland
- Advanced Magnetic Imaging Centre, Helsinki University of Technology, FI-02015 TKK, Espoo, Finland
- Department of Clinical Neurophysiology, Helsinki University Central Hospital, FI-00029 HUS, Helsinki, Finland

Received 5 January 2009; received in revised form 6 April 2009; accepted 16 April 2009. published online 18 May 2009.

Abstract

A recent study described for the first time a patient group that suffered from spontaneous chronic pain and from recurrent herpes simplex virus (HSV) infections. The patients had pain in widespread areas on one side of the body and were—due to subtle immunological abnormalities—susceptible to HSV infections. Although the clinical features of the pain suggested involvement of the central nervous system, supporting evidence for this was lacking. The objective of this study was to search for changes in the central nervous system that could account for the chronic pain in these patients. We monitored the central processing of pain and touch in eight patients and 11 healthy control subjects, who received painful heat and innocuous tactile stimuli to the hands during functional magnetic resonance imaging. Possible changes in the gray matter density of the brain were assessed with voxel-based morphometry. We found functional changes in the patients’ central pain circuitry: activation to heat pain was weaker than in control subjects in the insular cortices, anterior cingulate cortex (ACC), and thalamus, while the activations to innocuous tactile stimuli were similar in both groups. Gray matter density was decreased in the patients’ frontal and prefrontal cortices and in the ACC. The observed functional and structural changes in the central pain circuitry, together with the clinical features of the chronic pain support the hypothesis for central involvement in the development of chronic pain in these patients.

Keywords: Herpes simplex virus (HSV), Central pain, Functional magnetic resonance imaging (fMRI), Voxel-based morphometry (VBM)