Increased gray matter density in young women with chronic vulvar pain

Abstract Provoked vestibulodynia (PVD) is a common form of chronic vulvar pain with unknown aetiology. Central pain regulatory mechanisms have been suggested to be disrupted in PVD, and consequently, PVD may be associated with anatomical changes in pain modulatory brain areas. Here, we compared total gray matter volumes and regional gray matter densities between 14 medication‐free young women with relatively short‐standing PVD (1 to 9 yrs) and 14 control subjects using whole brain voxel‐based morphometry (VBM). VBM revealed that PVD subjects had significantly higher gray matter densities in pain modulatory and stress‐related areas, i.e. the parahippocampal gyrus/hippocampus and basal ganglia (globus pallidus, caudate nucleus, and substantia nigra). In several of these regions, gray matter was related to clinical symptoms, namely lowered pain thresholds and increased pain catastrophizing scores. No region showed decreased gray matter density in the PVD group. These results point at the morphological alterations in supra‐spinal pain modulatory circuitry, which might contribute to the clinical symptoms of patients with PVD. Previous VBM studies in older subjects with a longstanding chronic pain condition have demonstrated gray matter decreases in similar areas. We therefore speculate that gray matter density might increase in young pain patients with short disease duration and decrease in older subjects with longstanding disease, similarly to some psychiatric conditions, in which bi‐directional changes of gray matter have been observed.

[1]  C. L. Kwan,et al.  CORTICAL THINNING IN IBS: IMPLICATIONS FOR HOMEOSTATIC, ATTENTION, AND PAIN PROCESSING , 2008, Neurology.

[2]  Linda R Watkins,et al.  Beyond neurons: evidence that immune and glial cells contribute to pathological pain states. , 2002, Physiological reviews.

[3]  L. Rowland,et al.  Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder , 2002, Biological Psychiatry.

[4]  D. Buchwald,et al.  Comorbid clinical conditions in chronic fatigue , 2007, Journal of General Internal Medicine.

[5]  S. Waxman,et al.  Modulation of Thalamic Nociceptive Processing after Spinal Cord Injury through Remote Activation of Thalamic Microglia by Cysteine–Cysteine Chemokine Ligand 21 , 2007, The Journal of Neuroscience.

[6]  T. Joh,et al.  Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease , 2006, Experimental & Molecular Medicine.

[7]  W. A. Prado,et al.  An assessment of the antinociceptive and aversive effects of stimulating identified sites in the rat brain , 1985, Brain Research.

[8]  Scott R. Bishop,et al.  The Pain Catastrophizing Scale: Development and validation. , 1995 .

[9]  R. Mohney,et al.  Regional Difference in Susceptibility to Lipopolysaccharide-Induced Neurotoxicity in the Rat Brain: Role of Microglia , 2000, The Journal of Neuroscience.

[10]  S. Jabbur,et al.  Augmentation of nociceptive reflexes and chronic deafferentation pain by chemical lesions of either dopaminergic terminals or midbrain dopaminergic neurons , 1997, Brain Research.

[11]  T. Robinson,et al.  Widespread but regionally specific effects of experimenter‐ versus self‐administered morphine on dendritic spines in the nucleus accumbens, hippocampus, and neocortex of adult rats , 2002, Synapse.

[12]  Alan C. Evans,et al.  Automatic Quantification of MS Lesions in 3D MRI Brain Data Sets: Validation of INSECT , 1998, MICCAI.

[13]  R. Melzack The McGill Pain Questionnaire: Major properties and scoring methods , 1975, PAIN.

[14]  T. J. Nickola,et al.  Brain-derived TNFα mediates neuropathic pain , 1999, Brain Research.

[15]  R. Amsel,et al.  Vestibular tactile and pain thresholds in women with vulvar vestibulitis syndrome , 2002, Pain.

[16]  B. McEwen,et al.  Effects of adverse experiences for brain structure and function , 2000, Biological Psychiatry.

[17]  M. Meana,et al.  Dyspareunia: sexual dysfunction or pain syndrome? , 1997, The Journal of nervous and mental disease.

[18]  B. Conti,et al.  Stress induced morphological microglial activation in the rodent brain: Involvement of interleukin-18 , 2007, Neuroscience.

[19]  B. Condon,et al.  Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome , 2003, Neuroreport.

[20]  W. Maixner,et al.  A Conceptual Model for the Pathophysiology of Vulvar Vestibulitis Syndrome , 2006, Obstetrical & gynecological survey.

[21]  C. Woolf,et al.  The neuropathic pain triad: neurons, immune cells and glia , 2007, Nature Neuroscience.

[22]  J. Magnusson,et al.  The involvement of dopamine in nociception: the role of D1 and D2 receptors in the dorsolateral striatum , 2000, Brain Research.

[23]  Karl J. Friston,et al.  Correlation between structural and functional changes in brain in an idiopathic headache syndrome , 1999, Nature Medicine.

[24]  T. Jensen,et al.  The clinical picture of neuropathic pain. , 2001, European journal of pharmacology.

[25]  L. Fertitta,et al.  Vulvar vestibulitis syndrome. , 1992, Nurse practitioner forum.

[26]  D. Buchwald,et al.  Comorbid clinical conditions in chronic fatigue: a co-twin control study. , 2001, Journal of general internal medicine.

[27]  N. Avis,et al.  Chronic vulvar and other gynecologic pain: prevalence and characteristics in a self-reported survey. , 2006, The Journal of reproductive medicine.

[28]  E. Chudler,et al.  The role of the basal ganglia in nociception and pain , 1995, Pain.

[29]  Karl J. Friston,et al.  A unified statistical approach for determining significant signals in images of cerebral activation , 1996, Human brain mapping.

[30]  Emeran A. Mayer,et al.  Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis , 2005, Pain.

[31]  A. Apkarian,et al.  Chronic Back Pain Is Associated with Decreased Prefrontal and Thalamic Gray Matter Density , 2004, The Journal of Neuroscience.

[32]  Hanefi Yildirim,et al.  Volumetric MRI study of key brain regions implicated in obsessive–compulsive disorder , 2007, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[33]  L. Pinessi,et al.  Voxel‐Based Morphometry Reveals Gray Matter Abnormalities in Migraine , 2007, Headache.

[34]  M. Sullivan,et al.  Catastrophizing, pain, and disability in patients with soft-tissue injuries , 1998, Pain.

[35]  J. Chaves,et al.  Spontaneous cognitive strategies for the control of clinical pain and stress , 1987, Journal of Behavioral Medicine.

[36]  M. Joëls,et al.  Stress-induced changes in hippocampal function. , 2008, Progress in brain research.

[37]  D. Hellhammer,et al.  Psychological and endocrine correlates of chronic pelvic pain associated with adhesions. , 1999, Journal of psychosomatic obstetrics and gynaecology.

[38]  Y. Binik,et al.  A New Instrument for Pain Assessment in Vulvar Vestibulitis Syndrome , 2004, Journal of sex & marital therapy.

[39]  L. Wise,et al.  Prevalence and predictors of chronic lower genital tract discomfort. , 2001, American journal of obstetrics and gynecology.

[40]  Alain Dagher,et al.  Fibromyalgia patients show an abnormal dopamine response to pain , 2007, The European journal of neuroscience.

[41]  Patrice Boyer,et al.  Neuroplasticity: from MRI to depressive symptoms , 2004, European Neuropsychopharmacology.

[42]  Larry A. Tupler,et al.  Segmented Hippocampal Volume in Children and Adolescents with Posttraumatic Stress Disorder , 2006, Biological Psychiatry.

[43]  A Straube,et al.  Gray matter decrease in patients with chronic tension type headache , 2005, Neurology.

[44]  R. Luerding,et al.  Striatal grey matter increase in patients suffering from fibromyalgia – A voxel-based morphometry study , 2007, PAIN.

[45]  Caleb M. Adler,et al.  Voxel-Based Study of Structural Changes in First-Episode Patients with Bipolar Disorder , 2007, Biological Psychiatry.

[46]  U. Bogdahn,et al.  Subtle Grey Matter Changes Between Migraine Patients and Healthy Controls , 2008, Cephalalgia : an international journal of headache.

[47]  Alan C. Evans,et al.  Automated 3-D extraction and evaluation of the inner and outer cortical surfaces using a Laplacian map and partial volume effect classification , 2005, NeuroImage.

[48]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[49]  David A Seminowicz,et al.  Accelerated Brain Gray Matter Loss in Fibromyalgia Patients: Premature Aging of the Brain? , 2007, The Journal of Neuroscience.

[50]  Massimo Filippi,et al.  Brain Gray Matter Changes in Migraine Patients With T2-Visible Lesions: A 3-T MRI Study , 2006, Stroke.

[51]  David A. Williams,et al.  Evidence of augmented central pain processing in idiopathic chronic low back pain. , 2004, Arthritis and rheumatism.

[52]  T. J. Nickola,et al.  Brain-derived TNFalpha mediates neuropathic pain. , 1999, Brain research.

[53]  Bogdan Draganski,et al.  Decrease of thalamic gray matter following limb amputation , 2006, NeuroImage.

[54]  Bogdan Draganski,et al.  Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients , 2006, Pain.

[55]  M. Bushnell,et al.  Neural correlates of painful genital touch in women with vulvar vestibulitis syndrome , 2005, Pain.

[56]  I. Kirsch,et al.  Catastrophizing, depression and expectancies for pain and emotional distress , 2001, Pain.

[57]  Friedrich Eg Vulvar vestibulitis syndrome. , 1987, The Journal of reproductive medicine.