Tobias Schmidt-Wilcke

Gray matter decrease in patients with chronic tension type headache

Using MRI and voxel-based morphometry, the authors investigated 20 patients with chronic tension type headache (CTTH) and 20 patients with medication-overuse headache and compared them to 40 controls with no headache history. Only patients with CTTH demonstrated a significant gray matter decrease in regions known to be involved in pain processing. The finding implies that the alterations are specific to CTTH rather than a response to chronic head pain or chronification per se.

Affective components and intensity of pain correlate with structural differences in gray matter in chronic back pain patients

&NA; Although chronic back pain is one of the most frequent reasons for permanent impairment in people under 65, the neurobiological mechanisms of chronification remain vague. Evidence suggests that cortical reorganisation, so‐called functional plasticity, may play a role in chronic back pain patients. In the search for the structural counterpart of such functional changes in the CNS, we examined 18 patients suffering from chronic back pain with voxel‐based morphometry and compared them to 18 sex and age matched healthy controls. We found a significant decrease of gray matter in the brainstem and the somatosensory cortex. Correlation analysis of pain unpleasantness and the intensity of pain on the day of scanning revealed a strong negative correlation (i.e. a decrease in gray matter with increasing unpleasantness/increasing intensity of pain) in these areas. Additionally, we found a significant increase in gray matter bilaterally in the basal ganglia and the left thalamus. These data support the hypothesis that ongoing nociception is associated with cortical and subcortical reorganisation on a structural level, which may play an important role in the process of the chronification of pain.

Striatal grey matter increase in patients suffering from fibromyalgia – A voxel-based morphometry study

Abstract Fibromyalgia (FM), among other chronic pain syndromes, such as chronic tension type headache and atypical face pain, is classified as a so‐called dysfunctional pain syndrome. Patients with fibromyalgia suffer from widespread, “deep” muscle pain and often report concomitant depressive episodes, fatigue and cognitive deficits. Clear evidence for structural abnormalities within the muscles or soft tissue of fibromyalgia patients is lacking. There is growing evidence that clinical pain in fibromyalgia has to be understood in terms of pathological activity of central structures involved in nociception. We applied MR‐imaging and voxel‐based morphometry, to determine whether fibromyalgia is associated with altered local brain morphology. We investigated 20 patients with the diagnosis of primary fibromyalgia and 22 healthy controls. VBM revealed a conspicuous pattern of altered brain morphology in the right superior temporal gyrus (decrease in grey matter), the left posterior thalamus (decrease in grey matter), in the left orbitofrontal cortex (increase in grey matter), left cerebellum (increase in grey matter) and in the striatum bilaterally (increase in grey matter). Our data suggest that fibromyalgia is associated with structural changes in the CNS of patients suffering from this chronic pain disorder. They might reflect either a consequence of chronic nociceptive input or they might be causative to the pathogenesis of fibromyalgia. The affected areas are known to be both, part of the somatosensory system and part of the motor system.

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

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.

Subtle Grey Matter Changes Between Migraine Patients and Healthy Controls

Local morphological alterations of the brain have recently been detected in cluster headache and chronic tension-type headache, but not in migraine. We investigated 35 patients suffering from migraine and compared them with 31 healthy controls with no headache history. Using magnetic resonance imaging and voxel based morphometry, we found a significant decrease of grey matter in areas ascribable to the transmission of pain (cingulate cortex), but not in areas specific for migraine, such as the brainstem. Our data are in line with recent findings in chronic pain states, such as chronic phantom pain and chronic back pain. We suggest that the grey matter change in migraine patients is the consequence of frequent nociceptive input and should thus be reversible when migraine attacks cease.

Pregabalin rectifies aberrant brain chemistry, connectivity, and functional response in chronic pain patients.

Background:Chronic pain remains a significant challenge for modern health care as its pathologic mechanisms are largely unknown and preclinical animal models suffer from limitations in assessing this complex subjective experience. However, human brain neuroimaging techniques enable the assessment of functional and neurochemical alterations in patients experiencing chronic pain and how these factors may dynamically change with pharmacologic treatment. Methods:To identify the clinical action of pregabalin, a proven analgesic, the authors performed three complementary brain neuroimaging procedures: (proton magnetic resonance spectroscopy, functional magnetic resonance imaging, and functional connectivity magnetic resonance imaging) in 17 chronic pain patients diagnosed with fibromyalgia. Results:The authors found that pregabalin but not placebo reduces combined glutamate + glutamine levels within the posterior insula (pregabalin P = 0.016; placebo P = 0.71). Interestingly, reductions in clinical pain were associated with reductions in brain connectivity of this structure to brain regions within the default mode network during pregabalin (r = 0.82; P = 0.001) but not placebo (r = −0.13; P = 0.63). Response of default mode network regions to experimental pain was also reduced with pregabalin (P = 0.018) but not placebo (P = 0.182). Perhaps most importantly, baseline values for all three neuroimaging markers predicted subsequent analgesic response to pregabalin but not placebo. Conclusions:The results of this study suggest that pregabalin works in part by reducing insular glutamatergic activity, leading to a reduction of the increased functional connectivity seen between brain regions in chronic pain states. The study also supports a role for human brain imaging in the development, assessment, and personalized use of central-acting analgesics.

Reduced insular γ-aminobutyric acid in fibromyalgia

OBJECTIVE Recent scientific findings have reinvigorated interest in examining the role of γ-aminobutyric acid (GABA), the major inhibitory central nervous system neurotransmitter, in chronic pain conditions. Decreased inhibitory neurotransmission is a proposed mechanism in the pathophysiology of chronic pain syndromes such as fibromyalgia (FM). The purpose of this study was to test the hypothesis that decreased levels of insular and anterior cingulate GABA would be present in FM patients, and that the concentration of this neurotransmitter would be correlated with pressure-pain thresholds. METHODS Sixteen FM patients and 17 age- and sex-matched healthy controls underwent pressure-pain testing and a 3T proton magnetic resonance spectroscopy session in which the right anterior insula, right posterior insula, anterior cingulate, and occipital cortex were examined in subjects at rest. RESULTS GABA levels in the right anterior insula were significantly lower in FM patients compared with healthy controls (mean ± SD 1.17 ± 0.24 arbitrary institutional units versus 1.42 ± 0.32 arbitrary institutional units; P = 0.016). There was a trend toward increased GABA levels in the anterior cingulate of FM patients compared with healthy controls (P = 0.06). No significant differences between groups were detected in the posterior insula or occipital cortex (P > 0.05 for all comparisons). Within the right posterior insula, higher levels of GABA were positively correlated with pressure-pain thresholds in the FM patients (Spearmans rho = 0.63; P = 0.02). CONCLUSION Diminished inhibitory neurotransmission resulting from lower concentrations of GABA within the right anterior insula may play a role in the pathophysiology of FM and other central pain syndromes.

Fibromyalgia: from pathophysiology to therapy

Individuals with fibromyalgia generally experience chronic widespread pain, which can be accompanied by further symptoms including fatigue, sleep disturbances, cognitive dysfunction, anxiety and depressive episodes. As the recognition and diagnosis of fibromyalgia has improved, the availability of therapeutic options for patients has increased. Furthermore, research into the neurobiological mechanisms that contribute to the chronic pain and concomitant symptoms experienced by patients with fibromyalgia has advanced our understanding of this debilitating disorder. In this Review, we aim to provide an overview of existing pathophysiological concepts. The roles of biological and psychological stress, genetic factors, and pain and sensory processing in the pathophysiology of fibromyalgia and related conditions are discussed. In addition, pharmacological treatments, including monoamine modulators, calcium channel modulators and γ-aminobutyric acid modulators, as well as nonpharmacological treatment options are considered.

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

Summary Chronic pelvic pain, with and without endometriosis, is associated with changes in regional gray matter volume within the central pain system. 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.

Executive function in chronic pain patients and healthy controls: different cortical activation during response inhibition in fibromyalgia.

UNLABELLED The primary symptom of fibromyalgia (FM) is chronic, widespread pain; however, patients report additional symptoms including decreased concentration and memory. Performance-based deficits are seen mainly in tests of working memory and executive function. Neural correlates of executive function were investigated in 18 FM patients and 14 age-matched healthy controls during a simple Go/No-Go task (response inhibition) while they underwent functional magnetic resonance imaging (fMRI). Performance was not different between FM and healthy control, in either reaction time or accuracy. However, fMRI revealed that FM patients had lower activation in the right premotor cortex, supplementary motor area, midcingulate cortex, putamen and, after controlling for anxiety, in the right insular cortex and right inferior frontal gyrus. A hyperactivation in FM patients was seen in the right inferior temporal gyrus/fusiform gyrus. Despite the same reaction times and accuracy, FM patients show less brain activation in cortical structures in the inhibition network (specifically in areas involved in response selection/motor preparation) and the attention network along with increased activation in brain areas not normally part of the inhibition network. We hypothesize that response inhibition and pain perception may rely on partially overlapping networks, and that in chronic pain patients, resources taken up by pain processing may not be available for executive functioning tasks such as response inhibition. Compensatory cortical plasticity may be required to achieve performance on a par with control groups. PERSPECTIVE Neural activation (fMRI) during response inhibition was measured in fibromyalgia patients and controls. FM patients show lower activation in the inhibition and attention networks and increased activation in other areas. Inhibition and pain perception may use overlapping networks: resources taken up by pain processing may be unavailable for other processes.