Posterior Insular GABA Levels Inversely Correlate with the Intensity of Experimental Mechanical Pain in Healthy Subjects

Thiaucourt, Margot; Shabes, Polina; Schloss, Natalie; Sack, Markus; Baumgärtner, Ulf; Schmahl, Christian

doi:10.1016/j.neuroscience.2017.09.043

Cited by 13 publications

(8 citation statements)

References 41 publications

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“…26 A study of healthy subjects found that excitatory and inhibitory neurotransmitter levels and the ratio of glutamate/GABA levels in the posterior insula were related to individual differences in pain sensitivity. 27 Increased glutamate levels and reduced GABA levels were found within the insula of patients with fibromyalgia; insula glutamate was also greater in patients with diabetic neuropathy. 28,29 The altered balance of excitatory and inhibitory neurotransmitters in the insula may contribute to its hyperreactivity in chronic pain.…”

Section: Discussionmentioning

confidence: 92%

Altered functional connectivity of the insula in a rat model of recurrent headache

Jia¹,

Yu²,

Tang³

et al. 2020

Mol Pain

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Migraine is a pain disorder accompanied by various symptoms. The insula, a “cortical hub,” is involved in many functions. Few studies have focused on the insula in migraine. We explored the resting-state functional connectivity between the insula and other brain areas in rats subjected to repeated meningeal nociception which was commonly used as animal model of migraine. Inflammatory soup was infused through supradural catheters in conscious rats. The rats were subdivided based on the frequency of the inflammatory soup infusions. Magnetic resonance imaging data were acquired on rats 21 days after inflammatory soup infusion and functional connectivity seeded on the insula was analyzed. In the low-frequency inflammatory soup group, magnetic resonance imaging was performed again 1 h after the glyceryl trinitrate injection following baseline scanning. The cerebellum showed increased functional connectivity with the insula in the inflammatory soup groups. The insula showed increased functional connectivity with the medulla and thalamus in the ictal period in the low-frequency inflammatory soup rats. In the high-frequency inflammatory soup group, several areas showed increased functional connectivity with the insula, including the pons, midbrain, thalamus, temporal association cortex, and retrosplenial, visual, and sensory cortices. Our findings support the hypothesis that the headache phase of migraine depends on the activation and sensitization of the trigeminovascular system, and that the chronification of migraine may be related to higher brain centers and limbic cortices. The insula may be a new target for treatment of migraine.

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Section: Discussionmentioning

confidence: 92%

Altered functional connectivity of the insula in a rat model of recurrent headache

Jia¹,

Yu²,

Tang³

et al. 2020

Mol Pain

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“…These findings are consistent with previous research where GABA levels correlate with clinical pain severity 45 and experimental pain sensitivity. 49 In healthy younger individuals, acute experimental pain stimulation has been found to change GABA levels in various brain regions. 6 , 28 Specifically, administration of painful stimulation momentarily decreased GABA levels in the anterior cingulate and occipital cortex, 6 and tonic heat pain stimulation increased GABA levels in the prefrontal cortex.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown negative associations between GABA and chronic pain. 1 , 13 , 19 , 22 , 23 , 30 , 49 Similarly, acute pain stimulation leads to decreases in cerebral GABA and increases in Glx levels, 6 although this may depend on the experimental pain modality used. 28 However, most of the studies to date have included both younger and older individuals, raising the possibility that in older individuals, brain aging itself, and not chronic pain, may result in altered brain biochemistry.…”

Section: Introductionmentioning

confidence: 99%

Brain gamma-aminobutyric acid, but not glutamine and glutamate levels are lower in older adults with chronic musculoskeletal pain: considerations by sex and brain location

Cruz-Almeida

Forbes

Cohen

et al. 2021

PR9

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“…We suggest that this increased connectivity is required to actively suppress activity in regions known to contribute to pain processing, as previously reported for these tasks ( Schulz et al, 2019 ). We do not know the nature of such regional suppression; however, there are GABAergic neurons in subregions of the insular cortex ( Watson, 2016 ; Thiaucourt et al, 2018 ), and these might possibly contribute. Besides the general observation of increased connectivity, which is linked to higher task performance and lower pain, each cognitive intervention has its own pattern of intra-cortical connectivity.…”

Section: Discussionmentioning

confidence: 99%

Ultra-high-field imaging reveals increased whole brain connectivity underpins cognitive strategies that attenuate pain

Schulz

Stankewitz

Winkler

et al. 2020

eLife

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We investigated how the attenuation of pain with cognitive interventions affects brain connectivity using neuroimaging and a whole brain novel analysis approach. While receiving tonic cold pain, 20 healthy participants performed three different pain attenuation strategies during simultaneous collection of functional imaging data at 7 tesla. Participants were asked to rate their pain after each trial. We related the trial-by-trial variability of the attenuation performance to the trial-by-trial functional connectivity strength change of brain data. Across all conditions, we found that a higher performance of pain attenuation was predominantly associated with higher functional connectivity. Of note, we observed an association between low pain and high connectivity for regions that belong to brain regions long associated with pain processing, i.e. the insular and cingulate cortices. For one of the cognitive strategies (safe place), the performance of pain attenuation was explained by diffusion tensor imaging metrics of increased white matter integrity.

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Posterior Insular GABA Levels Inversely Correlate with the Intensity of Experimental Mechanical Pain in Healthy Subjects

Cited by 13 publications

References 41 publications

Altered functional connectivity of the insula in a rat model of recurrent headache

Altered functional connectivity of the insula in a rat model of recurrent headache

Brain gamma-aminobutyric acid, but not glutamine and glutamate levels are lower in older adults with chronic musculoskeletal pain: considerations by sex and brain location

Ultra-high-field imaging reveals increased whole brain connectivity underpins cognitive strategies that attenuate pain

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