Spatial extent of pain influences gray matter volume in fibromyalgia patients.

Aim of Investigation: Fibromyalgia (FS) is a syndrome characterised by chronic widespread pain, whose pathophysiology is still controversial. Previous studies assessing alterations in local gray matter volume (GMV) in FS have obtained somewhat inconsistent results, possibly due to differences in clinical features. Our aim was to assess GMV changes in FS compared to a control group, and their correlations with the severity of clinical aspects, including illness duration, pain intensity and quality, body pain area, number of positive tender points and depression. Methods: Thirty-four women with FS diagnosed by a rheumatologist and 38 healthy women (controls, C) without chronic pain matched for age (FS: range 18-55 ys, mean 44; C: 25-60 ys, mean 45.6), menopausal status, educational level, handedness and caffeine consumption, participated in the study. The control subjects had experienced no pain (N=9) or episodic/recurrent pain without (N=20) or with use of pain killers (N=9) over the past year. Depressive symptoms were assessed using the Center for Epidemiology Studies-Depression Scale (CES-D); the sensory (S), affective (A) and evaluative (E) quality of spontaneous pain were tested using the Italian adaptation of the McGill Pain Questionnaire (Questionario Italiano del Dolore - QUID). Spatial extent of pain was assessed using Margolis body pain area drawings. Pressure pain thresholds were measured by means of an algometer applied to the 18 defining tender points and to 10 additional points to obtain a detailed picture of spatial distribution of allodynia. A high-resolution structural T1-weighted brain scan (360 sagittal slices without gap; isotropic voxel size 0.5mm; FOV 240 x 240 x 180mm; TR 35ms; flip angle 50; TE 5.7ms) was acquired for each subject, using a 3T Philips Achieva MR scanner. GMV was assessed applying voxel-based morphometry Oasis, The Online Abstract Submission System http://www.abstractsonline.com/submit/SubmitPrin... 1 of 3 03/07/2014 01:46 PM International Association for the Study of Pain 1510 H Street NW, Suite 600 Washington, DC 20005-1020 USA Phone: +1-202-524-5300 (VBM) to modulated data in SPM8 using the VBM8 toolbox (voxel-wise critical p < 0.005; cluster size corrected for multiple comparisons using AlphaSim with 10,000 Monte Carlo simulations). Results: Patients showed no significant differences in GMV compared to the total control group. In the patient sample, GMV was negatively correlated with QUID-E score in BA 6 and with the spatial extent of spontaneous pain in the bilateral parahippocampal gyrus (pHG), and it was positively correlated with illness duration in the cerebellum. GMV was independent of pain intensity, tender point count, CES-D, QUID-S and QUID-A score. Reported pain extent ranged from 9-90% of body surface (mean/median: 48%). Patients with below-median pain extent had greater GMV than patients with above-median values in the bilateral pHG and cerebellum, left paracentral lobule (BA 6) and cingulate gyrus (BA 31). GMV values of the controls in these brain areas were intermediate between the two patient groups. Spatial extent of pain was positively correlated with tender point count and with QUID-S and was independent of all other clinical and nuisance variables included in the study. Conclusions: Some, but not all, previous VBM studies have reported reduced GMV in the pHG and in the cingulate cortex in FS (Wood, 2010). Our results point to a possible explanation for these inconsistent findings: depending on how widespread their pain, FS patients may show either reduced or increased GMV in the pHG and cingulate cortex, i.e. they are more different from each other than from the control group. Further research is needed to explore the possible causes