The brain changes

The nervous system is plastic meaning that it changes and moulds according to the stimuli presented. Norman Doidge wrote about the ‘brain that changes itself’ and we have seen over the past 10 years or so an increasing number of studies that show this in a range of conditions, some painful and others not. Our ability to change and adapt have been a vital characteristics for our survival and to learn new skills. The same principles apply when we think about rehabilitation and treatment of painful conditions. We need to tap into these properties and stimulate the brain and other body systems (e.g. immune system, neuroendocrine) so that we are creators of health manifesting physically through normal movement, function and optimal performance.

Here are some examples of studies that have shown brain changes using functional MRI. You will note the variety that includes rheumatoid arthritis, osteoarthritis, pain, chronic pelvic pain, schizophrenia and fibromyalgia. This has serious implications for treatment in that we need brain focused therapies as well as those that target the tissues and end-organs. This includes the absolute need to explain pain and symptoms from a neuroscience perspective.

Arthritis Rheum. 2012 Feb;64(2):371-9. doi: 10.1002/art.33326.

Structural changes of the brain in rheumatoid arthritis.

Wartolowska K, Hough MG, Jenkinson M, Andersson J, Wordsworth BP, Tracey I.

Abstract

OBJECTIVE: To investigate whether structural changes are present in the cortical and subcortical gray matter of the brains of patients with rheumatoid arthritis (RA).

METHODS: We used two surface-based style morphometry analysis programs and a voxel-based style analysis program to compare high-resolution structural magnetic resonance imaging data obtained for 31 RA patients and 25 age- and sex-matched healthy control subjects.

RESULTS: We observed an increase in gray matter content in the basal ganglia of RA patients, mainly in the nucleus accumbens and caudate nucleus. There were no differences in the cortical gray matter. Moreover, patients had a smaller intracranial volume.

CONCLUSION: Our results suggest that RA is associated with changes in the subcortical gray matter rather than with cortical gray matter atrophy. Since the basal ganglia play an important role in motor control as well as in pain processing and in modulating behavior in response to aversive stimuli, we suggest that these changes may result from altered motor control or prolonged pain processing. The differences in brain volume may reflect either generalized atrophy or differences in brain development.

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Am J Psychiatry. 2002 Feb;159(2):244-50.

Volume changes in gray matter in patients with schizophrenia.

Hulshoff Pol HE, Schnack HG, Bertens MG, van Haren NE, van der Tweel I, Staal WG, Baaré WF, Kahn RS.

Abstract

OBJECTIVE: Schizophrenia is generally characterized by a progressive decline in functioning. Although structural brain abnormalities, particularly decrements in gray matter volume, are considered important to the pathology of schizophrenia, it is not resolved whether the brain abnormalities become more prominent over time.

METHOD: Magnetic resonance brain images from 159 patients with schizophrenia and 158 healthy comparison subjects between 16 and 70 years of age were compared. Using linear regression analysis, the authors analyzed the relationship between the volumes of the total brain, gray and white matter, cerebellum, and lateral and third ventricles with patient age.

RESULTS: Total brain (-2.2%), cerebral gray matter (-3.3%), prefrontal gray matter (-4.4%), and prefrontal white matter (-3.5%) volumes were smaller, and lateral (27%) and third (30%) ventricle and peripheral CSF (11%) volumes were larger in schizophrenia patients. A significant group-by-age interaction for gray matter volume was found, as shown by a steeper regression slope between age and gray matter volume in patients (-3.43 ml/year) than in healthy comparison subjects (-2.74 ml/year).

CONCLUSIONS: The smaller brains of the patients with schizophrenia can be explained by decreases in gray matter volume. Moreover, the finding that the smaller gray matter volume was more pronounced in older patients with schizophrenia may suggest progressive loss of cerebral gray matter in schizophrenia patients.

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Psychosom Med. 2009 Jun;71(5):566-73. Epub 2009 May 4.

Decreased gray matter volumes in the cingulo-frontal cortex and the amygdala in patients with fibromyalgia.

Burgmer M, Gaubitz M, Konrad C, Wrenger M, Hilgart S, Heuft G, Pfleiderer B.

Abstract

OBJECTIVE: Studies in fibromyalgia syndrome with functional neuroimaging support the hypothesis of central pain augmentation. To determine whether structural changes in areas of the pain system are additional preconditions for the central sensitization in fibromyalgia we performed voxel based morphometry in patients with fibromyalgia and healthy controls.

METHODS: We performed 3 Tesla magnetic resonance imaging of the brain in 14 patients with fibromyalgia and 14 healthy controls. Regional differences of the segmented and normalized gray matter volumes in brain areas of the pain system between both groups were determined. In those areas in which patients structurally differed from healthy controls, the correlation of disease-related factors with gray matter volumes was analyzed.

RESULTS: Patients presented a decrease in gray matter volume in the prefrontal cortex, the amygdala, and the anterior cingulate cortex (ACC). The duration of pain or functional pain disability did not correlate with gray matter volumes. A trend of inverse correlation of gray matter volume reduction in the ACC with the duration of pain medication intake has been detected.

CONCLUSIONS: Our results suggest that structural changes in the pain system are associated with fibromyalgia. As disease factors do not correlate with reduced gray matter volume in areas of the cingulo-frontal cortex and the amygdala in patients, one possible interpretation is that volume reductions might be a precondition for central sensitization in fibromyalgia.

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Brain. 2008 Dec;131(Pt 12):3222-31. Epub 2008 Sep 26.

Working memory performance is correlated with local brain morphology in the medial frontal and anterior cingulate cortex in fibromyalgia patients: structural correlates of pain-cognition interaction.

Luerding R, Weigand T, Bogdahn U, Schmidt-Wilcke T.

Abstract

Fibromyalgia (FM) is a disorder of unknown aetiology, characterized by chronic widespread pain, stiffness and sleep disturbances. In addition, patients frequently complain of memory and attention deficits. Accumulating evidence suggests that FM is associated with CNS dysfunction and with an altered brain morphology. However, few studies have specifically investigated neuropsychological issues in patients suffering from FM. We therefore sought to determine whether neuropsychological deficits found in FM patients may be correlated with changes in local brain morphology specifically in the frontal, temporal or cingulate cortices. Twenty FM patients underwent extensive testing for potential neuropsychological deficits, which demonstrated significantly reduced working memory and impaired non-verbal long-term memory (limited to free recall condition) in comparison with normative data from age- and education-matched control groups. Voxel-based morphometry (VBM) was used to evaluate for potential correlations between test results and local brain morphology. Performance on non-verbal working memory was positively correlated with grey matter values in the left dorsolateral prefrontal cortex, whereas performance on verbal working memory (digit backward) was positively correlated with grey matter values in the supplementary motor cortex. On the other hand, pain scores were negatively correlated with grey matter values in the medial frontal gyrus. White matter analyses revealed comparable correlations for verbal working memory and pain scores in the medial frontal and prefrontal cortex and in the anterior cingulate cortex. Our data suggest that, in addition to chronic pain, FM patients suffer from neurocognitive deficits that correlate with local brain morphology in the frontal lobe and anterior cingulate gyrus, which may be interpreted to indicate structural correlates of pain-cognition interaction.

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Pain. 2012 May;153(5):1006-14. Epub 2012 Mar 2.

Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study.

As-Sanie S, Harris RE, Napadow V, Kim J, Neshewat G, Kairys A, Williams D, Clauw DJ, Schmidt-Wilcke T.

Abstract

Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15%-20% of women in the United States. Endometriosis is often associated with CPP, however, other factors, such as preexisting or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing. Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, and 23 healthy controls. All patients with endometriosis and/or CPP were surgically confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception, including the left thalamus, left cingulate gyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis who had no CPP. We conclude that CPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis.

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Arthritis Rheum. 2010 Oct;62(10):2930-40.

Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty: a longitudinal voxel-based morphometric study.

Gwilym SE, Filippini N, Douaud G, Carr AJ, Tracey I.

Abstract

OBJECTIVE: Voxel-based morphometry (VBM) is a method of assessing brain gray matter volume that has previously been applied to various chronic pain conditions. From this previous work, it appears that chronic pain is associated with altered brain morphology. The present study was undertaken to assess these potential alterations in patients with painful hip osteoarthritis (OA).

METHODS: We studied 16 patients with unilateral right-sided hip pain, before and 9 months after hip arthroplasty. This enabled comparison of gray matter volume in patients with chronic musculoskeletal pain versus healthy controls, as well as identification of any changes in volume following alleviation of pain (after surgery). Assessment involved self-completion questionnaires to assess pain, function, and psychosocial variables, and magnetic resonance imaging scanning of the brain for VBM analysis.

RESULTS: Significant differences in brain gray matter volume between healthy controls and patients with painful hip arthritis were seen. Specifically, areas of the thalamus in patients with chronic OA pain exhibited decreased gray matter volume. Furthermore, when these preoperative changes were compared with the brain morphology of the patients 9 months after surgery, the areas of reduced thalamic gray matter volume were found to have “reversed” to levels seen in healthy controls.

CONCLUSION: Our findings confirm that gray matter volume decreases within the left thalamus in the presence of chronic pain and disability in patients with hip OA. The results also show that these thalamic volume changes reverse after hip arthroplasty and are associated with decreased pain and increased function. These findings have potential implications with regard to optimizing the timing of orthopedic interventions such as arthroplasty

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