Elsevier

NeuroImage

Volume 54, Issue 2, 15 January 2011, Pages 1315-1323
NeuroImage

1H-MR spectroscopic detection of metabolic changes in pain processing brain regions in the presence of non-specific chronic low back pain

https://doi.org/10.1016/j.neuroimage.2010.09.039Get rights and content

Abstract

Reliable detection of metabolic changes in the brain in vivo induced by chronic low back pain may provide improved understanding of neurophysiological mechanisms underlying the manifestation of chronic pain. In the present study, absolute concentrations of N-acetyl-aspartate (NAA), creatine (Cr), total choline (tCho), myo-inositol (mI), glutamate (Glu) and glutamine (Gln) were measured in three different pain processing cortical regions (anterior insula, anterior cingulate cortex, and thalamus) of ten patients with non-specific chronic low back pain by means of proton MR spectroscopy (1H-MRS) and compared to matched healthy controls. Significant decrease of Glu was observed in the anterior cingulate cortex of patients. Patients also revealed a trend of decreasing Gln concentrations in all investigated brain areas. Reductions of NAA were observed in the patient group in anterior insula and in anterior cingulated cortex, whereas mI was reduced in anterior cingulated cortex and in thalamus of patients. Reduced concentrations of Glu and Gln may indicate disordered glutamatergic neurotransmission due to prolonged pain perception, whereas decrease of NAA and mI may be ascribed to neuron and glial cell loss. No significant changes were found for Cr. The morphological evaluation of anatomic brain data revealed a significantly decreased WM volume of 17% (p < 0.05) as well as a non significant trend for GM volume increase in the anterior insula of patients.

Research Highlights

1H-MRS provides a means of detecting chronic pain related metabolic changes in brain. ►Decreased Glu/Gln in pain patients' anterior cingulum (aCC) and insula (aI). ►Evidence for cell loss due to reduced NAA and mI in patients' aCC, aI and thalamus. ►Reduced white matter volume in pain patients' aI and aCC. ►Evidence for gray matter volume increase in patients' aI.

Introduction

Chronic low back pain (CLBP) represents one of the rife forms of pain disease in Western industrial countries (Andersson, 1999). In most cases, CLBP leads to substantial decline of life quality of affected persons and their capabilities, and also frequently triggers depression, anxiety states or other mental disorders. CLBP is associated with high direct and indirect costs for healthcare systems due to potential invalidity and lifelong therapy (Dagenais et al., 2008). One particularly critical point is the lack of precise knowledge about the origins and causes of CLBP. In fact, the real challenge is to distinguish serious spinal pathology from non-specific low back pain (Rubinstein and Van Tulder, 2008). In Western Europe only 10% of CLBP cases can be ascribed to defined pathological disorders, like injuries of nerves or muscles, intervertebral disc prolapses or inflammatory processes. For the remaining 90% of patients, whose back pain cannot be attributed to any pathomorphological cause, the disease is characterised as non-specific chronic low back pain (nCLBP) (Krismer and Van Tulder, 2007). Consequently, therapeutic approaches are also non-specific and therefore often less efficient. Improved understanding of the pathological origins underlying the manifestation of chronic pain may thus help to develop specific preventive or therapeutic methods for managing CLBP (Borsook et al., 2007).

One of the frequently discussed hypotheses why pain turns from an acute to a chronic state assumes hypersensitisation of pain processing networks in the central nervous system that are managing the input assessment of peripheral nociceptive receptors (Brooks and Tracey, 2005, Borsook et al., 2007, Tracey and Bushnell, 2009). Application of modern imaging methods, like functional magnetic resonance imaging (fMRI) or positron emission tomography (PET), have already revealed new insights into the functional and spatial aspects of cerebral pain processing in humans (Peyron et al., 2000, Apkarian et al., 2005). In addition, recent studies performed on humans in vivo with proton magnetic resonance spectroscopy (1H-MRS) have suggested that neuronal activations are accompanied by spectroscopically detectable biochemical changes in the presence of acute pain (Gussew et al., 2010a, Kupers et al., 2009, Mullins et al., 2005). It may thus be supposed that biochemical changes also play a crucial role in the manifestation of chronic pain (Lin et al., 2010, Prescot et al., 2009, Harris et al., 2008, Harris et al., 2009, Siddall et al., 2006, Fukui et al., 2006, Dichgans et al., 2005, Grachev et al., 2002a, Grachev et al., 2002b, Pattany et al., 2002). There is, however, still a significant lack of knowledge about these changes in specific pain processing brain regions, including neurotransmitter dysfunctions that may be potentially related to chronic pain.

In the present study, 1H-MRS was performed in three different, pain processing cortical regions of nCLBP patients and compared to matched healthy controls to explore metabolic differences due to non-specific chronic low back pain.

Section snippets

Description of patient population

We examined two groups of persons, the first consisting of two male and eight female nCLBP patients (right-handed, age: 22–52 years, weight: 52–83 kg, body height: 160–180 cm), and the second comprising ten healthy controls that were pairwise matched to the patients with respect to gender, age, body weight and height. All persons were recruited through advertisement in the local press. Patients underwent detailed clinical history evaluation conducted by a pain physiologist to unravel potential

Results

All spectra showed high spectral resolution and sufficient SNR (see Table 1). The FWHMNAA (in Hz), which was calculated automatically by the LCModel, represents the full linewidth at half maximum of the CH3-singlet of NAA at 2.01 ppm. The SNRNAA value was calculated by taking the ratio between the baseline corrected NAA peak amplitude and twice the standard deviation of the spectrum's residuals that remained after subtraction of the fitted results from the original spectrum (Provencher, 1993).

Discussion

The major aim of our study was to investigate whether 1H-MRS spectroscopy, a non-invasive technique for biochemical tissue assessment in vivo, allows quantification of metabolic changes associated with chronic low back pain in human brain areas that are known to be involved in cortical pain processing. We used single-voxel 1H-MR spectroscopy at 3T, which is less affected by mislocalisation artefacts compared to 1H-MR spectroscopic imaging techniques that may suffer, for example, from signal

Conclusion

In conclusion, the results of this study indicate a role of 1H-MRS to assess nCLBP induced metabolic changes in the human central nervous system (CNS) to explore mechanisms underlying the manifestation of chronic pain. Despite the relatively small sample size and different durations and intensities of pain perception in the patient group, we observed changes of several brain metabolites, which may potentially be used as diagnostic markers for assessment of chronic pain disease. Especially, the

Acknowledgments

This study was supported by the Centre for Interdisciplinary Prevention of Diseases Related to Professional Activities (Kompetenzzentrum für Interdisziplinäre Prävention, KIP) founded by the Friedrich-Schiller-University Jena and the Accident Prevention and Insurance Association for Food and Restaurants (Berufsgenossenschaft Nahrungsmittel und Gaststätten, BGN, Germany). A.G. acknowledges support from a stipend funded by KIP (project 1.1.29). This study was also supported by the Bernstein Group

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