Changes in brain gray matter due to repetitive painful stimulation

Using functional imaging, we recently investigated how repeated painful stimulation over several days is processed, perceived and modulated in the healthy human brain. Considering that activation-dependent brain plasticity in humans on a structural level has already been demonstrated in adults, we were interested in whether repeated painful stimulation may lead to structural changes of the brain. 14 healthy subjects were stimulated daily with a 20 min pain paradigm for 8 consecutive days, using structural MRI performed on days 1, 8, 22 and again after 1 year. Using voxel based morphometry, we are able to show that repeated painful stimulation resulted in a substantial increase of gray matter in pain transmitting areas, including mid-cingulate and somatosensory cortex. These changes are stimulation dependent, i.e. they recede after the regular nociceptive input is stopped. This data raises some interesting questions regarding structural plasticity of the brain concerning the experience of both acute and chronic pain.

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

[2]  P. Wall,et al.  Textbook of pain , 1989 .

[3]  R Melzack,et al.  Central Neuroplasticity and Pathological Pain , 2001, Annals of the New York Academy of Sciences.

[4]  S. McMahon,et al.  Role of the Immune system in chronic pain , 2005, Nature Reviews Neuroscience.

[5]  C. Büchel,et al.  Habituation to painful stimulation involves the antinociceptive system , 2007, Pain.

[6]  A. May Chronic pain may change the structure of the brain , 2008, PAIN®.

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

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

[9]  H. Flor,et al.  Remote activation of referred phantom sensation and cortical reorganization in human upper extremity amputees , 2003, Experimental Brain Research.

[10]  Bogdan Draganski,et al.  Neuroplasticity: Changes in grey matter induced by training , 2004, Nature.

[11]  Rie Suzuki,et al.  Enlargement of the Receptive Field Size to Low Intensity Mechanical Stimulation in the Rat Spinal Nerve Ligation Model of Neuropathy , 2000, Experimental Neurology.

[12]  Christian Gaser,et al.  Magnetic resonance-based morphometry: a window into structural plasticity of the brain , 2006, Current opinion in neurology.

[13]  B. Neundörfer,et al.  Patterns of cortical reorganization in complex regional pain syndrome , 2003, Neurology.

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

[15]  Niels Birbaumer,et al.  Peripheral and electrocortical responses to painful and non-painful stimulation in chronic pain patients, tension headache patients and healthy controls , 2004, Neuroscience Letters.

[16]  J. Kenemans,et al.  Processing capacity in chronic pain patients: A visual event-related potentials study , 2006, Pain.

[17]  H. Flor,et al.  Effect of sensory discrimination training on cortical reorganisation and phantom limb pain , 2001, The Lancet.

[18]  Karl J. Friston,et al.  Cerebral Asymmetry and the Effects of Sex and Handedness on Brain Structure: A Voxel-Based Morphometric Analysis of 465 Normal Adult Human Brains , 2001, NeuroImage.

[19]  H. Fruhstorfer,et al.  Method for quantitative estimation of thermal thresholds in patients. , 1976, Journal of neurology, neurosurgery, and psychiatry.

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

[21]  Niels Birbaumer,et al.  The role of operant conditioning in chronic pain: an experimental investigation , 2002, Pain.

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

[23]  H. Flor Cortical reorganisation and chronic pain: implications for rehabilitation. , 2003, Journal of rehabilitation medicine.

[24]  Christian Gaser,et al.  Differ between Musicians and NonMusicians , 2003 .

[25]  Michael Schröder,et al.  Bilateral thalamic gray matter changes in patients with restless legs syndrome , 2005, NeuroImage.

[26]  B. Neundörfer,et al.  Cortical reorganization during recovery from complex regional pain syndrome , 2004, Neurology.

[27]  M. Koltzenburg The changing sensitivity in the life of the nociceptor , 1999, Pain.

[28]  T. Gordh,et al.  Spinal nerve lesion alters blood–spinal cord barrier function and activates astrocytes in the rat , 2006, Pain.

[29]  C. Woolf,et al.  Neuronal plasticity: increasing the gain in pain. , 2000, Science.

[30]  A. May,et al.  Structural brain alterations following 5 days of intervention: dynamic aspects of neuroplasticity. , 2007, Cerebral cortex.

[31]  H. Dinse,et al.  Mean sustained pain levels are linked to hemispherical side-to-side differences of primary somatosensory cortex in the complex regional pain syndrome I , 2004, Experimental Brain Research.

[32]  Oye Gureje,et al.  Psychiatric aspects of pain , 2007, Current opinion in psychiatry.

[33]  M. Peters,et al.  Chronic low back pain and the reaction to repeated acute pain stimulation , 1989, Pain.

[34]  J. Schoenen,et al.  Deficient habituation of evoked cortical potentials in migraine: a link between brain biology, behavior and trigeminovascular activation? , 1996, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.