Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study

Grachev, Igor D.; Fredrickson, Bruce E.; Apkarian, A. Vania

doi:10.1016/s0304-3959(00)00340-7

Cited by 269 publications

(193 citation statements)

References 35 publications

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“…In this study, the location of the probes measured changes in the dorsal and lateral prefrontal cortex (DLPC). Functional and other imaging studies of pain have suggested an important role of this area of the brain in both acute (Svensson et al, 1997;Becerra et al, 1999;Becerra et al, 2001) and chronic pain conditions (Grachev et al, 2000;Apkarian et al, 2004). A number of projections that are received by the prefrontal cortex originate in visual, auditory, parietal and cingulate regions, as well as subcortical regions such as the amygdala (Barbas, 2000) and hypothalamus (RempelClower and Barbas, 1998).…”

Section: Activation In the Frontal Regionmentioning

confidence: 99%

Diffuse optical tomography of pain and tactile stimulation: Activation in cortical sensory and emotional systems

et al. 2008

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Using Diffuse Optical Tomography (DOT) we detected activation in the somatosensory cortex and frontal brain areas following tactile (brush) and noxious heat stimulation. Healthy volunteers received stimulation to the dorsum of the right hand. In the somatosensory cortex area, tactile stimulation produced a robust, contralateral to the stimulus, hemodynamic response with a weaker activation on the ipsilateral side. For the same region, noxious thermal stimuli produced bilateral activation of similar intensity that had a prolonged activation with a two-peak similar to results have been reported with functional MRI. Bilateral activation was observed in the frontal areas, oxyhemoglobin changes were positive for brush stimulation while they were initially negative (contralateral) for heat stimulation. These results suggest that based on the temporal and spatial characteristics of the response in the sensory cortex, it is possible to discern painful from mechanical stimulation using DOT. Such ability might have potential applications in a clinical setting in which pain needs to be assessed objectively (e.g. analgesic efficacy, pain responses during surgery).

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Section: Activation In the Frontal Regionmentioning

confidence: 99%

Diffuse optical tomography of pain and tactile stimulation: Activation in cortical sensory and emotional systems

et al. 2008

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“…All spectra were transformed into a standardized scale using the Scion Image analysis package (Scion Corp, Frederick, MD, USA) and analyzed as described earlier. [36][37][38][39] The relative concentrations of NAA (the dominant peak in 1 H-MR spectra, positioning at 2.02 parts per million (ppm)) were meas-ured relative to the peak of creatine/phosphocreatine complex (this creatine/phosphocreatine complex we label as Cr (3.0 ppm; internal standard)). The rationale for using the ratios method relative to Cr has been explained.…”

Section: Molecular Psychiatrymentioning

confidence: 99%

“…In our previous studies of different cognitive states (studies of anxiety, 36,37 pain, 38 anxiety and pain 39 ) using in vivo proton magnetic resonance spectroscopy ( 1 H-MRS), we demonstrated a sensitivity of the method for documentation of chemical-perceptual characteristics of the human personality, which can be captured by monitoring the regional changes of neuronal marker N-acetyl aspartate (NAA) in relation to specific cognitive measures. These studies already demonstrated that this approach could become a new method for tracking the long-term brain chemical characteristics of anxiety and pain, and, possibly some other cognitive states.…”

Section: Introductionmentioning

confidence: 99%

“…42,43 Thus, any changes in neuronal density/function and/or synaptic connections in the ACC of normal subjects might affect the SCW interference level (hypothesis to be tested). (2) NAA is a sensitive marker for several other cognitive states (depression (manuscript in preparation), anxiety and pain [36][37][38][39]. (3) This chemical is changed the most in neuropsychiatric disorders with abnormal interference (eg schizophrenia, 44,45 Alzheimer's disease, 46 bipolar disorder, 47 and anxiety disorders [48][49][50] ).…”

Section: Introductionmentioning

confidence: 99%

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Cognitive interference is associated with neuronal marker N-acetyl aspartate in the anterior cingulate cortex: an in vivo 1H-MRS study of the Stroop Color-Word task

et al. 2001

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The neurobiology of cognitive interference is unknown. Previous brain imaging studies using the Stroop Color-Word (SCW) task indicate involvement of the cingulate cortex cognitive division. The present study examines interrelationships between regional brain N-Acetyl aspartate (NAA) levels (as identified by in vivo proton magnetic resonance spectroscopy in the right and left anterior cingulate cortex (ACC), dorsolateral prefrontal cortex, orbitofrontal cortex and thalamus) and cognitive interference (as measured by the SCW task) in 15 normal subjects. The results show that brain chemistry depends on cognitive interference levels (high vs low). Reduction of NAA levels was demonstrated in the right ACC (ie, cognitive midsupracallosal division) of high interference subjects, as compared to the low interference group (P Ͻ 0.01, two-tailed t-test). Chemical-cognitive relationships were analyzed by calculating correlations between regional NAA levels and the SCW task scores. Cognitive interference was highly correlated with the right anterior cingulate NAA (r = 0.76, P Ͻ 0.001), and was unrelated to other studied regional NAA, including the left ACC (P Ͻ 0.025; comparing the difference between r values in the right and left ACC). The interrelationships between NAA across brain regions were examined using correlation analysis (square matrix correlation maps), which detected different connectivity patterns between the two groups. These findings provide evidence of ACC involvement in cognitive interference suggesting a possibility of neuronal reorganization in the physiological mechanism of interference (most likely due to genetically predetermined control of the number of neurons, dendrites and receptors, and their function). We conclude that spectroscopic brain mapping of NAA, the marker of neuronal density and function, to the SCW task measures differentiates between high and low interference in normal subjects. This neuroimaging/cognitive tool may be useful for documentation of interference in studying cognitive control mechanisms, and in diagnosis of neuropsychiatric disorders where dysfunction of cingulate cortex is expected. Molecular Psychiatry (2001) 6, 529-539.

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“…This has been exploited in a study of patients with chronic low back pain that showed a decrease in NAA concentration within the dorsolateral prefrontal cortex. It remains to be determined how useful MRS is for assessing efficacy of drug action in pain patients; however, as the changes in metabolite profiles in chronic back pain patients were related to certain subjective measures on the McGill pain questionnaire (21), it might prove yet to be a useful noninvasive measure of drug efficacy.…”

Section: Potential Solutions That Could Improve Drug Developmentmentioning

confidence: 99%

Pharmacological FMRI in the development of new analgesic compounds

2006

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Chronic pain is a major problem for the individual and for society. Despite a range of drugs being available to treat chronic pain, only inadequate pain relief can be achieved for many patients. There is therefore a need for the development of new analgesic compounds. The assessment of pain depends to date entirely on the subjective report of the patient, in contrast to many other clinical conditions where biomarkers that help determine the severity and stage of the disease enable the physician to monitor the course of the disease and treatment effects longitudinally. In this article, we illustrate that magnetic resonance-based imaging techniques have the potential to provide sensitive and specific biomarkers of the pain experience, as well as clarifying disease mechanisms. Functional magnetic resonance imaging (FMRI) is particularly suited to investigating the effects of pharmacological agents on pain processing within the human central nervous system. Combination of FMRI and drug administration is termed pharmacological FMRI (phFMRI). In addition to outlining several methodological considerations that have to be taken into account when performing phFMRI, we discuss phFMRI studies that have already used this technique to study the effects of analgesic compounds. These studies provide promising data for the use of phFMRI as sensitive tool in assessing a potential drug effect. Such pharmacodynamic readouts obtained early in the process of drug development would not only save the pharmaceutical industry substantial amounts of money, but would also avoid the unnecessary exposure of patients to molecules with limited or no therapeutic value. We are therefore optimistic that phFMRI will be used as a tool with high sensitivity and specificity for evaluating analgesic agents in early drug development and clinicalstudies.

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Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study

Cited by 269 publications

References 35 publications

Diffuse optical tomography of pain and tactile stimulation: Activation in cortical sensory and emotional systems

Diffuse optical tomography of pain and tactile stimulation: Activation in cortical sensory and emotional systems

Cognitive interference is associated with neuronal marker N-acetyl aspartate in the anterior cingulate cortex: an in vivo 1H-MRS study of the Stroop Color-Word task

Pharmacological FMRI in the development of new analgesic compounds

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