***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Summary . The neurobiology of the interaction between pain and anxiety is unknown . The present study examined interrelationships between : regional brain chemistry ( as identified by in vivo proton magnetic resonance spectroscopy [ 1H-MRS ] in dorsolateral prefrontal cortex [ DLPFC ] , orbitofrontal cortex [ OFC ] , cingulate and thalamus ) , pain ( as measured by short form of the McGill Pain Question naire [ SF-MPQ ] ) , and anxiety ( measured by the State-Trait Anxiety Inventory )  in chronic low back pain ( CLBP ) patients , and contrasted to the relationship between brain chemistry and anxiety in sex and age-matched normal subjects . The results show that brain chemistry depends on a 3-way interaction of brain regions examined , subject groups ( normal vs. CLBP ) , and anxiety levels ( high vs. low ) . The concentration of N-Acetyl aspartate ( the largest peak in 1H-MRS ) in OFC could distinguish between anxiety levels and between subject groups . Chemical-perceptual relationships were analyzed by calculating correlations between regional chemicals and perceptual measures of pain and anxiety . To isolate pain from anxiety , these maps were subdivided based on anxiety and , in the CLBP patients along anxiety-more-related vs. anxiety-less-related pain descriptors and along sensory vs. affective pain descriptors . There was a precise relationship between perception and brain chemistry . The chemical-perceptual network best related to pain in CLBP patients was comprised of the DLPFC and OFC ; the chemical-anxiety network was best related to the OFC chemistry in normals and to all four regions studied in CLBP patients ; and the cingulate was best related to the affective component of pain . We conclude that the chemical-perceptual mapping differentiates between closely related perceptual states of pain and anxiety in chronic pain and provides a brain regional-chemical-perceptual description of the long-term reorganization that occurs with chronic pain Functional neuroimaging studies in humans have shown that nociceptive stimuli elicit activity in a wide network of cortical areas commonly labeled as the " pain matrix " and thought to be preferentially involved in the perception of pain . Despite the fact that this " pain matrix " has been used extensively to build models of where and how nociception is processed in the human brain , convincing experimental evidence demonstrating that this network is specifically related to nociception is lacking . The aim of the present study was to determine whether there is at least a subset of the " pain matrix " that responds uniquely to nociceptive somatosensory stimulation . In a first experiment , we compared the fMRI brain responses elicited by a  r and om sequence of brief nociceptive somatosensory , non-nociceptive somatosensory , auditory and visual stimuli  , all presented within a similar attentional context . We found that the fMRI responses triggered by nociceptive stimuli can be largely explained by a combination of ( 1 ) multimodal neural activities ( i.e. , activities elicited by all stimuli regardless of sensory modality ) and ( 2 ) somatosensory-specific but not nociceptive-specific neural activities ( i.e. , activities elicited by both nociceptive and non-nociceptive somatosensory stimuli ) . The magnitude of multimodal activities correlated significantly with the perceived saliency of the stimulus . In a second experiment , we compared these multimodal activities to the fMRI responses elicited by auditory stimuli presented using an oddball paradigm . We found that the spatial distribution of the responses elicited by novel non-target and novel target auditory stimuli resembled closely that of the multimodal responses identified in the first experiment . Taken together , these findings suggest that the largest part of the fMRI responses elicited by phasic nociceptive stimuli reflects non nociceptive-specific cognitive processes It is well known that multiple sclerosis ( MS ) pathogenesis continues even during periods of clinical silence . To quantify the metabolic characteristics of this activity we compared the absolute levels of  N-acetylaspartate ( NAA ) , creatine ( Cr ) , and choline ( Cho ) in the normal-appearing white matter ( NAWM ) between relapsing-remitting ( RR ) MS patients and controls .  Metabolite concentrations were obtained with 3D proton MR spectroscopy at 1.5 T in a 480 cm(3 ) volume-of-interest ( VOI ) , centered on the corpus callosum of 11 MS patients and 9 matched controls .  Gray/white-matter/cerebral-spinal-fluid ( CSF ) volumes were obtained from MRI segmentation . Patients ' average VOI tissue volume ( V(T ) ) , 410.8 + /- 24.0 cm(3 ) , and metabolite levels , NAA = 6.33 + /- 0.70 , Cr = 4.67 + /- 0.52 , Cho = 1.40 + /- 0.17 mM , were different from the controls by -8 % , -9 % , + 22 % and + 32 % . The Cho level was the only single metric differentiating patients from controls at 100 % specificity and > 90 % sensitivity . Diffusely elevated Cho and Cr probably reflect widespread microscopic inflammation , gliosis , or de- and remyelination in the NAWM . Both metabolites are potential prognostic indicators of current disease activity , preceding NAA decline and atrophy Quantitative single-voxel , short echo-time ( TE ) MR spectroscopy ( MRS ) was used to determine metabolite concentrations in the cerebral normal-appearing white matter ( NAWM ) of 76 patients with multiple sclerosis ( MS ) , and the WM of 25 controls . In NAWM of all MS disease types ( primary progressive , relapsing-remitting , and secondary progressive ) , the concentration ratio of total N-acetyl-aspartate (tNAA)/total creatine ( tCr ) was decreased compared to controls . Remarkably , this was entirely due to an increase of tCr in MS patients , whereas there was no difference in tNAA . Separate quantification of the two tNAA components yielded no significant difference in NAA ( N-acetyl-aspartate ) , while the concentration of NAAG ( N-acetyl-aspartyl-glutamate ) was slightly-but significantly-elevated in MS patients . Myo-inositol ( Ins ) was strongly increased in MS patients , and choline-containing compounds ( Cho ) were mildly increased . There were no metabolite differences between disease types , and no correlations with disability scores . The results are supported by measures of spectral quality , which were identical for patients and controls . In conclusion , MS NAWM containing very little perilesional tissue is characterized by increased glial cell numbers ( increase of Ins and tCr ) without evidence of axonal dysfunction ( normal NAA ) . Further studies should eluci date the mechanism underlying increased NAAG in MS NAWM Study Design . Cost of illness study alongside a r and omized controlled trial . Objective . To describe the costs of care for patients with low back pain ( 1 ) and to identify patient characteristics as predictors for high health care cost during a 1-year follow-up ( 2 ) . Summary of Background Data . Low back pain ( LBP ) is one of the leading causes of high health care costs in industrialized countries ( Life time prevalence , 70 % ) . A lot of research has been done to improve primary health care and patients ′ prognosis . However , the cost of health care does not necessarily follow changes in patient outcomes . Methods . General practitioners ( n = 126 ) recruited 1378 patients consulting for LBP .  Sociodemographic data , pain characteristics , and LBP-related cost data  were collected by interview at baseline and after 6 and 12 months . Costs were evaluated from the societal perspective . Predictors of high cost during the subsequent year were studied using logistic regression analysis . Results . Mean direct and indirect costs for LBP care are about twice as high for patients with chronic LBP compared to acutely ill patients . Indirect costs account for more than 52 % to 54 % of total costs . About 25 % of direct costs refer to therapeutic procedures and hospital or rehabilitational care .  Patients with high disability and limitations in daily living  show a 2- to 5-fold change for subsequent high health care costs . Depression seems to be highly relevant for direct health care utilization . Conclusion . Interventions design ed to reduce high health care costs for LBP should focus on patients with severe LBP and depressive comorbidity . Our results add to the economic underst and ing of LBP care and may give guidance for future actions on health care improvement and cost reduction & 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 
    Output:
    
Conclusion This review provides evidence for alterations in the biochemical profile of the brain in patients with CLBP , which suggests that biochemical changes may play a significant role in the development and pathophysiology of CLBP and shed light on the development of new treatments for CLBP