Dataset Information

Cingulate GABA levels inversely correlate with the intensity of ongoing chronic knee osteoarthritis pain.

ABSTRACT:

Background

This study aims to investigate the role of the mid-anterior cingulate cortex ?-aminobutyric acid levels in chronic nociceptive pain. The molecular mechanisms of pain chronification are not well understood. In fibromyalgia, low mid-anterior cingulate cortex ?-aminobutyric acid was associated with high pain suggesting a role of prefrontal disinhibition. We hypothesize that mid-anterior cingulate cortex GABAergic disinhibition may underpin chronic pain independent of the pain etiology and comorbid negative affect. Proton magnetic resonance spectra were acquired at 3T from the mid-anterior cingulate cortex in 20 patients with chronic painful knee osteoarthritis, and 19 healthy pain-free individuals using a point resolved spectroscopy sequence optimized for detection of ?-aminobutyric acid. Participants underwent questionnaires for negative affect (depression and anxiety) and psychophysical pain phenotyping.

Results

No differences in mid-anterior cingulate cortex ?-aminobutyric acid or other metabolite levels were detected between groups. Ratings of perceived intensity of ongoing osteoarthritis pain were inversely correlated with ?-aminobutyric acid (r = -0.758, p < 0.001), but no correlations were seen for negative affect or pain thresholds. The pain ?-aminobutyric acid interrelation remained strong when controlling for depression (r = -0.820, p < 0.001). Combined levels of glutamine and glutamate were unrelated to psychometric or to pain thresholds.

Conclusion

Our study supports mid-anterior cingulate cortex ?-aminobutyric acid as a potential marker of pain severity in chronic nociceptive pain states independent of negative affect. The findings suggest that GABAergic disinhibition of the salience network may underlie sensitization to averse stimuli as a mechanism contributing to pain chronification.

SUBMITTER: Reckziegel D

PROVIDER: S-EPMC4956171 | biostudies-literature | 2016 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

Cingulate GABA levels inversely correlate with the intensity of ongoing chronic knee osteoarthritis pain.

Reckziegel Diane D Raschke Felix F Cottam William J WJ Auer Dorothee P DP

Molecular pain 20160101

<h4>Background</h4>This study aims to investigate the role of the mid-anterior cingulate cortex γ-aminobutyric acid levels in chronic nociceptive pain. The molecular mechanisms of pain chronification are not well understood. In fibromyalgia, low mid-anterior cingulate cortex γ-aminobutyric acid was associated with high pain suggesting a role of prefrontal disinhibition. We hypothesize that mid-anterior cingulate cortex GABAergic disinhibition may underpin chronic pain independent of the pain eti ...[more]

PMID: 27206661

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Project description:BackgroundAn imbalance between inhibitory and excitatory neurometabolites has been implicated in chronic pain. Prior work identified elevated levels of Gamma-aminobutyric acid + macromolecules ("GABA+") using magnetic resonance spectroscopy (MRS) in people with migraine. What is not understood is whether this increase in GABA+ is a cause, or consequence of living with, chronic migraine. Therefore, to further elucidate the nature of the elevated GABA+ levels reported in migraine, this study aimed to observe how GABA+ levels change in response to changes in the clinical characteristics of migraine over time.MethodsWe observed people with chronic migraine (ICHD-3) over 3-months as their treatment was escalated in line with the Australian Pharmaceutical Benefits Scheme (PBS). Participants underwent an MRS scan and completed questionnaires regarding migraine frequency, intensity (HIT-6) and disability (WHODAS) at baseline and following the routine 3 months treatment escalation to provide the potential for some participants to recover. We were therefore able to monitor changes in brain neurochemistry as clinical characteristics potentially changed over time.ResultsThe results, from 18 participants who completed both baseline and follow-up measures, demonstrated that improvements in migraine frequency, intensity and disability were associated with an increase in GABA+ levels in the anterior cingulate cortex (ACC); migraine frequency (r = - 0.51, p = 0.03), intensity (r = - 0.51, p = 0.03) and disability (r = - 0.53, p = 0.02). However, this was not seen in the posterior cingulate gyrus (PCG). An incidental observation found those who happened to have their treatment escalated with CGRP-monoclonal antibodies (CGRP-mAbs) (n = 10) had a greater increase in ACC GABA+ levels (mean difference 0.54 IU IQR [0.02 to 1.05], p = 0.05) and reduction in migraine frequency (mean difference 10.3 IQR [2.52 to 18.07], p = 0.01) compared to those who did not (n = 8).ConclusionThe correlation between an increase in ACC GABA+ levels with improvement in clinical characteristics of migraine, suggest previously reported elevated GABA+ levels may not be a cause of migraine, but a protective mechanism attempting to suppress further migraine attacks.

Project description:ImportanceThigh muscle weakness is associated with knee discomfort and osteoarthritis disease progression. Little is known about the efficacy of high-intensity strength training in patients with knee osteoarthritis or whether it may worsen knee symptoms.ObjectiveTo determine whether high-intensity strength training reduces knee pain and knee joint compressive forces more than low-intensity strength training and more than attention control in patients with knee osteoarthritis.Design, setting, and participantsAssessor-blinded randomized clinical trial conducted at a university research center in North Carolina that included 377 community-dwelling adults (≥50 years) with body mass index (BMI) ranging from 20 to 45 and with knee pain and radiographic knee osteoarthritis. Enrollment occurred between July 2012 and February 2016, and follow-up was completed September 2017.InterventionsParticipants were randomized to high-intensity strength training (n = 127), low-intensity strength training (n = 126), or attention control (n = 124).Main outcomes and measuresPrimary outcomes at the 18-month follow-up were Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) knee pain (0 best-20 worst; minimally clinically important difference [MCID, 2]) and knee joint compressive force, defined as the maximal tibiofemoral contact force exerted along the long axis of the tibia during walking (MCID, unknown).ResultsAmong 377 randomized participants (mean age, 65 years; 151 women [40%]), 320 (85%) completed the trial. Mean adjusted (sex, baseline BMI, baseline outcome values) WOMAC pain scores at the 18-month follow-up were not statistically significantly different between the high-intensity group and the control group (5.1 vs 4.9; adjusted difference, 0.2; 95% CI, -0.6 to 1.1; P = .61) or between the high-intensity and low-intensity groups (5.1 vs 4.4; adjusted difference, 0.7; 95% CI, -0.1 to 1.6; P = .08). Mean knee joint compressive forces were not statistically significantly different between the high-intensity group and the control group (2453 N vs 2512 N; adjusted difference, -58; 95% CI, -282 to 165 N; P = .61), or between the high-intensity and low-intensity groups (2453 N vs 2475 N; adjusted difference, -21; 95% CI, -235 to 193 N; P = .85). There were 87 nonserious adverse events (high-intensity, 53; low-intensity, 30; control, 4) and 13 serious adverse events unrelated to the study (high-intensity, 5; low-intensity, 3; control, 5).Conclusions and relevanceAmong patients with knee osteoarthritis, high-intensity strength training compared with low-intensity strength training or an attention control did not significantly reduce knee pain or knee joint compressive forces at 18 months. The findings do not support the use of high-intensity strength training over low-intensity strength training or an attention control in adults with knee osteoarthritis.Trial registrationClinicalTrials.gov Identifier: NCT01489462.

Dataset Information

Cingulate GABA levels inversely correlate with the intensity of ongoing chronic knee osteoarthritis pain.

Background

Results

Conclusion

Publications

Cingulate GABA levels inversely correlate with the intensity of ongoing chronic knee osteoarthritis pain.

Similar Datasets

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