Brain Metabolite Changes in the Anterior Cingulate Cortex of Chronic Low Back Pain Patients and Correlations Between Metabolites and Psychological State

Kameda, Takuya; Fukui, Sei; Tominaga, Ryoji; Sekiguchi, Miho; Iwashita, Narihito; Ito, Kazuki; Tanaka‐Mizuno, Sachiko; Konno, Satoshi

doi:10.1097/ajp.0000000000000583

Cited by 24 publications

(33 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 19 , 20 Moreover relatively low levels of NAA are also found in some chronic conditions that have chronic pain components, including diabetic painful neuropathy, chronic neuropathic pain, and chronic low back pain. 11 , 12 , 21 Thus, it is reasonable to hypothesize that individuals with chronic pain might have lower concentrations of NAA in the ACC, relative to healthy participants. 11 , 12 Consistent with a role for this metabolite in chronic pain, research has found a positive correlation between NAA levels and pain thresholds.…”

Section: Discussionmentioning

confidence: 99%

“… 11 , 12 , 21 Thus, it is reasonable to hypothesize that individuals with chronic pain might have lower concentrations of NAA in the ACC, relative to healthy participants. 11 , 12 Consistent with a role for this metabolite in chronic pain, research has found a positive correlation between NAA levels and pain thresholds. 10 However, our study found that tDCS could increase concentration levels of NAA.…”

Section: Discussionmentioning

confidence: 99%

“… 5 , 7 , 8 Consistent with the notion of Glu as an activating neurotransmitter, research has shown higher concentrations of Glu in the ACC of individuals with chronic pain, relative to healthy subjects. 11 , 12 Such increases could be associated with the brain’s attempts to activate inhibition processes. Our study found increases in glutamate levels in the ACC after tDCS treatment, and that this elevation was associated with pain reduction.…”

Section: Discussionmentioning

confidence: 99%

“… 9 , 10 For example, pain intensity has been shown to be associated with higher Glu and low NAA levels. 11 , 12 Elevated levels of Cho have also been found in ACC in individuals with pelvic pain syndrome, relative to healthy subjects. 13 Based on these findings, it can be hypothesized that alterations in brain metabolites, specifically elevations in concentration of Gln combined Glu (Glx), NAA, and Cho in the ACC are associated with elevations in pain.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The effects of transcranial direct current stimulation on metabolite changes at the anterior cingulate cortex in neuropathic pain: a pilot study

Auvichayapat¹,

Keeratitanont²,

Janyachareon³

et al. 2018

JPR

View full text Add to dashboard Cite

BackgroundNeuropathic pain (NP) in individuals with spinal cord injury (SCI) is both common and highly refractory to treatment. Primary motor cortex stimulation can relieve pain by interrupting the transmission of noxious information of descending pain modulatory systems including the anterior cingulate cortex (ACC). Previous research has shown that transcranial direct current stimulation (tDCS) can produce pain relief in individuals with NP. However, the underlying mechanisms for these effects are not yet understood. Research findings suggest the possibility that changes in brain metabolite concentrations produced by tDCS might explain some of these effects. For example, previous research has shown that SCI-related NP is associated with elevated levels of glutamine combined glutamate (Glx) per creatine (Glx/Cr). In addition, decreased N-acetylaspartate (NAA) has been observed in the ACC in individuals with chronic pain.MethodsWe used magnetic resonance spectroscopy (MRS) to study changes in NAA and Glx levels in the ACC after tDCS treatment. Ten patients with SCI with NP were given five daily anodal tDCS sessions, and an MRS evaluation was performed before and after treatment.ResultsThe results showed treatment-related reductions in pain, and increases in both Glx/Cr and NAA/Cr in the ACC. The observed increase in NAA/Cr is consistent with the possibility that tDCS improves the descending pain modulation system by increasing the neuronal activity in the ACC.ConclusionThe findings suggest the possibility that tDCS’s beneficial effects on neuropathic pain may be due, at least in part, to the changes it produces in Glx/Cr and NAA/Cr levels in the ACC. Additional research with larger samples sizes and a control group to evaluate this possibility is warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The effects of transcranial direct current stimulation on metabolite changes at the anterior cingulate cortex in neuropathic pain: a pilot study

Auvichayapat¹,

Keeratitanont²,

Janyachareon³

et al. 2018

JPR

View full text Add to dashboard Cite

show abstract

“…Chronic pelvic pain patients had significantly lower levels of NAA/creatine (Cr) in the primary motor cortex compared with healthy patients [ 9 ]. And, chronic low back pain (CLBP) patients showed lower NAA levels and higher glutamate (Glu)+glutamine (Gln)/Cr and Glu+Gln (Glx)/mL ratios in the anterior cingulate cortex (ACC) of CLBP patients compared with controls [ 10 ]. CLBP patients showed significant decrease in Glu in patients’ ACC and reduced ml in the ACC and thalamus [ 11 ], decreased choline (Cho) in the right somatosensory cortex [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Peripheral and Central Metabolites Affecting Depression, Anxiety, Suicidal Ideation, and Anger in Complex Regional Pain Syndrome Patients Using a Magnetic Resonance Spectroscopy: A Pilot Study

Jung

Kim

Jeon

et al. 2018

Psychiatry Investig

View full text Add to dashboard Cite

Objective This study investigated peripheral and central metabolites affecting depression, anxiety, suicidal ideation, and anger in complex regional pain syndrome (CRPS) patients. Methods Metabolite levels were determined in the right and left thalamus and insula, in 12 CRPS patients using magnetic resonance spectroscopy (MRS). Results There were positive correlations between valine (Val)/tNAA (N-acetylaspartate+N-acetylaspartylglutamate) and the anxiety, and a negative correlation between glutamine (Gln)/NAA and the depression. There were positive correlations between alanine (Ala)/Gln and the depression and suicidal ideation, between glutamate (Glu)/Gln and the depression and suicidal ideation, between N-acetylaspartylglutamate (NAAG)/Gln and the depression. There was a positive correlation between Ala/NAAG and the trait anger and a negative correlation between creatine (Cr)/N-acetylaspartate (NAA) and the trait anger. There was a negative correlation between Cr/Glx (Glu+Gln) and the trait anger. High hemoglobin and alkaline phosphatase were associated with low pain levels, but CO2 and chloride showed positive correlations with pain levels in CRPS patients. Peripheral glucose, CO2 and chloride were associated with depression, anxiety, anger and suicidal ideation. Conclusion The specific central and peripheral metabolites were associated with psychological disorders including depression, anxiety, suicidal ideation and anger in CRPS patients, showing pathological interactions between a painful body and mind.

show abstract

3D magnetic resonance spectroscopic imaging reveals links between brain metabolites and multidimensional pain features in fibromyalgia

Lee

Andronesi

Torrado‐Carvajal

et al. 2021

European Journal of Pain

View full text Add to dashboard Cite

Background: Fibromyalgia is a centralized multidimensional chronic pain syndrome, but its pathophysiology is not fully understood. Methods: We applied 3D magnetic resonance spectroscopic imaging (MRSI), covering multiple cortical and subcortical brain regions, to investigate the association between neuro-metabolite (e.g. combined glutamate and glutamine, Glx; myo-inositol, mIno; and combined (total) N-acetylaspartate and N-acetylaspartylglutamate, tNAA) levels and multidimensional clinical/behavioural variables (e.g. pain catastrophizing, clinical pain severity and evoked pain sensitivity) in women with fibromyalgia (N = 87). Results: Pain catastrophizing scores were positively correlated with Glx and tNAA levels in insular cortex, and negatively correlated with mIno levels in posterior cingulate cortex (PCC). Clinical pain severity was positively correlated with Glx levels in insula and PCC, and with tNAA levels in anterior midcingulate cortex (aMCC), but negatively correlated with mIno levels in aMCC and thalamus. Evoked pain sensitivity was negatively correlated with levels of tNAA in insular cortex, MCC, PCC and thalamus. Conclusions: These findings support single voxel placement targeting nociceptive processing areas in prior 1 H-MRS studies, but also highlight other areas not as commonly targeted, such as PCC, as important for chronic pain pathophysiology. Identifying target brain regions linked to multidimensional symptoms of fibromyalgia (e.g. negative cognitive/affective response to pain, clinical pain, evoked pain sensitivity) may aid the development of neuromodulatory and individualized therapies.Furthermore, efficient multi-region sampling with 3D MRSI could reduce the burden of lengthy scan time for clinical research applications of molecular brain-based mechanisms supporting multidimensional aspects of fibromyalgia. Significance: This large N study linked brain metabolites and pain features in fibromyalgia patients, with a better spatial resolution and brain coverage, to understand a molecular mechanism underlying pain catastrophizing and other aspects of pain

show abstract

Brain Metabolite Changes in the Anterior Cingulate Cortex of Chronic Low Back Pain Patients and Correlations Between Metabolites and Psychological State

Cited by 24 publications

References 53 publications

The effects of transcranial direct current stimulation on metabolite changes at the anterior cingulate cortex in neuropathic pain: a pilot study

The effects of transcranial direct current stimulation on metabolite changes at the anterior cingulate cortex in neuropathic pain: a pilot study

Peripheral and Central Metabolites Affecting Depression, Anxiety, Suicidal Ideation, and Anger in Complex Regional Pain Syndrome Patients Using a Magnetic Resonance Spectroscopy: A Pilot Study

3D magnetic resonance spectroscopic imaging reveals links between brain metabolites and multidimensional pain features in fibromyalgia

Contact Info

Product

Resources

About