Increased brain responses during subjectively-matched mechanical pain stimulation in fibromyalgia patients as evidenced by MEG Ceferino Maestu a,c,⇑ , Alvaro Cortes a , Jose Manuel Vazquez a , David del Rio a,b , Jose María Gomez-Arguelles c , Francisco del Pozo a , Angel Nevado a,b a Centre for Biomedical Technology (CTB), Technical University of Madrid (UPM), Spain b Basic Psychology Department II, Complutense University of Madrid, Spain c Neuromadrid Clinical Centre, Madrid, Spain article info Article history: Accepted 25 September 2012 Available online 31 October 2012 Keywords: Fibromyalgia Central pain MEG Mechanical stimulation Event related fields highlights  Fibromyalgia patients showed increased brain responses with respect to controls during subjectively- matched painful mechanical stimulation.  Increased activity was found in somatosensory, temporal and parietal areas at short latencies and in prefrontal areas at both short and long latencies.  Therefore, central pain augmentation in fibromyalgia is not only present when patients and controls are subjected to the same level of stimulation but also occurs when stimulation is adjusted to produce similar subjective levels of pain in both groups. abstract Objective: The precise pathophysiology of fibromyalgia, a syndrome characterized by chronic widespread pain, remains to be clarified. When subjected to the same amount of stimulation, patients show enhanced brain responses as compared to controls, providing evidence of central pain augmentation in this syn- drome. We aimed to characterize brain response differences when stimulation is adjusted to elicit similar subjective levels of pain in both groups. Methods: Magnetoencephalography (MEG) was used to investigate the brain responses to pressure stim- ulation applied both above and below the pain threshold in nine patients and nine control subjects. A device was developed to deliver pressure pulses in a quantifiable and precise manner. The amount of pressure was adjusted to produce similar subjective pain in both groups. Results: A between-group comparison of differences between responses evoked by stimulation above and below the pain threshold was performed using cluster-based permutation testing. Increases in signal amplitude in somatosensory, temporal and parietal areas at short latencies, and in prefrontal areas at both short and long latencies, were found to be larger for patients than for control subjects. Conclusion: Fibromyalgia patients show enhanced brain responses after reducing the amount of pressure to produce similar subjective levels of pain than to the control subjects. Significance: The present results suggest that central pain augmentation is present in fibromyalgia, not only when the objective level of stimulation is kept the same as for control subjects, but also when stim- ulation is adjusted to produce similar levels of pain in patients and controls. Ó 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction Fibromyalgia (FMS) is a syndrome characterized by chronic widespread musculoskeletal pain, mood and sleep disorders and daytime fatigue (Abeles et al., 2007; Merskey and Bogduk, 1994) as defined by the American College of Rheumatology (ACR) 1990 classification criteria (Wolfe et al., 1990). Recently, the use of a pain index and a symptom severity rating have been recom- mended for diagnosis confirmation (Wolfe et al., 2010). FMS affects approximately 2% of the population: 3.4% of women and 0.5% of men (Wolfe et al., 1995). Studies of experimentally induced pain demonstrate that these patients have a lower pain threshold, as lower intensity stimuli are 1388-2457/$36.00 Ó 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2012.09.015 ⇑ Corresponding author at: Centre for Biomedical Technology, Campus de Montegancedo, Universidad Politécnica de Madrid, 28223 Pozuelo de Alarcón, Madrid, Spain. Tel.: +34 913364655; fax: +34 913366828. E-mail address: ceferino.maestu@ctb.upm.es (C. Maestu). Clinical Neurophysiology 124 (2013) 752–760 Contents lists available at SciVerse ScienceDirect Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph