Hyper-connectivity between the left motor cortex and prefrontal cortex is associated with the severity of dysfunction of the descending pain modulatory system in fibromyalgia

Franco, Álvaro de Oliveira; Fernandes, Camila; Vicunha, Paul; Bandeira, Janete Shatkoski; Aratanha, Maria Adelia; Torres, Iraci Lucena da Silva; Fregni, Felipe; Caumo, Wolnei

doi:10.1101/2021.02.11.430747

Cited by 3 publications

(3 citation statements)

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“…FM patients seem to have a deficit in the GABAergic network, represented by central sensitization and altered motor cortical excitability. (Caumo et al, 2016;de Oliveira Franco et al, 2022). This inhibitory dysfunction seems to be modulated by some interventions such as exercise, pregabalin, and non-invasive brain stimulation, which can increase intracortical inhibition (Pacheco-Barrios et al, 2022).…”

Section: Ici Fibromyalgia (Fm) and Major Depressive Disorder (Mdd)mentioning

confidence: 99%

Editorial: Bench to Bedside – the translation of intracortical inhibition marker to clinical practice

Pimenta

Lima

Slawka

et al. 2023

ppcrj

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Section: Ici Fibromyalgia (Fm) and Major Depressive Disorder (Mdd)mentioning

confidence: 99%

Editorial: Bench to Bedside – the translation of intracortical inhibition marker to clinical practice

Pimenta

Lima

Slawka

et al. 2023

ppcrj

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“…Flodin et al 9 showed a decreased connectivity between the thalamus and premotor areas, and the right insula and primary sensorimotor areas, indicating reduced intrinsic coupling between pain-related brain regions and the primary sensorimotor areas in the absence of externally applied pain. Moreover, FM patients seem to have an unbalanced GABAergic network associated with central sensitization and altered motor cortical excitability 10 , 11 . Thus, measurements of sensorimotor system excitability and central sensitization are useful options for the identification of FM biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Motor cortex inhibition as a fibromyalgia biomarker

Pacheco‐Barrios

Lima

Pimenta

et al. 2022

Brain Network and Modulation

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Fibromyalgia (FM) is a common and refractory chronic pain condition with multiple clinical phenotypes. The current diagnosis is based on a syndrome identification which can be subjective and lead to under or over-diagnosis. Therefore, there is a need for objective biomarkers for diagnosis, phenotyping, and prognosis (treatment response and follow-up) in fibromyalgia. Potential biomarkers are measures of cortical excitability indexed by transcranial magnetic stimulation (TMS). However, no systematic analysis of current evidence has been performed to assess the role of TMS metrics as a fibromyalgia biomarker. Therefore, this study aims to evaluate evidence on corticospinal and intracortical motor excitability in fibromyalgia subjects and to assess the prognostic role of TMS metrics as response biomarkers in FM. We conducted systematic searches on PubMed/Medline, Embase, and Cochrane Central databases for observational studies and randomized controlled trials on fibromyalgia subjects that used TMS as an assessment. Three reviewers independently selected and extracted the data. Then, a random-effects model meta-analysis was performed to compare fibromyalgia and healthy controls in observational studies. Also, to compare active versus sham treatments, in randomized controlled trials. Correlations between changes in TMS metrics and clinical improvement were explored. The quality and evidence certainty were assessed following standardized approaches. We included 15 studies (696 participants, 474 FM subjects). The main findings were: (1) fibromyalgia subjects present less intracortical inhibition (mean difference (MD) = −0.40, 95% confidence interval (CI) −0.69 to −0.11) and higher resting motor thresholds (MD = 6.90 μV, 95% CI 4.16 to 9.63 μV) when compared to controls; (2) interventions such as exercise, pregabalin, and non-invasive brain stimulation increased intracortical inhibition (MD = 0.19, 95% CI 0.10 to 0.29) and cortical silent period (MD = 14.92 ms, 95% CI 4.86 to 24.98 ms), when compared to placebo or sham stimulation; (3) changes on intracortical excitability are correlated with clinical improvements – higher inhibition moderately correlates with less pain, depression, and pain catastrophizing; lower facilitation moderately correlates with less fatigue. Measures of intracortical inhibition and facilitation indexed by TMS are potential diagnostic and treatment response biomarkers for fibromyalgia subjects. The disruption in the intracortical inhibitory system in fibromyalgia also provides additional evidence that fibromyalgia has some neurophysiological characteristics of neuropathic pain. Treatments inducing an engagement of sensorimotor systems (e.g., exercise, motor imagery, and non-invasive brain stimulation) could restore the cortical inhibitory tonus in FM and induce clinical improvement.

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“…The descending pain modulatory system (DPMS) facilitates or inhibits pain, comprising cortical and subcortical CNS regions such as the ventrolateral periaqueductal grey, rostroventral medulla, and anterior cingulate cortex, among other regions, with significant involvement of the prefrontal cortex (PFC) and motor cortex (MC) 7 , 8 . We previously reported that the dysfunction of the DPMS in women with FM was associated with higher functional connectivity (FC) between the left MC and bilateral PFC assessed by functional near-infrared spectroscopy (fNIRS) 9 . Higher severity of FM symptoms has been associated with dysfunction of the DPMS 10 , the latter assessed by a standardized quantitative psychophysical protocol known as the conditioned pain modulation (CPM) test 7 , 10 .…”

Section: Introductionmentioning

confidence: 99%

Functional connectivity response to acute pain assessed by fNIRS is associated with BDNF genotype in fibromyalgia: an exploratory study

Franco

Venturini

Alves

et al. 2022

Sci Rep

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Fibromyalgia is a heterogenous primary pain syndrome whose severity has been associated with descending pain modulatory system (DPMS) function and functional connectivity (FC) between pain processing areas. The brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism has been linked to vulnerability to chronic pain. In this cross-sectional imaging genetics study, we investigated fibromyalgia, the relationship between BDNF Val66Met heterozygous genotypes (Val/Met), and the functional connectivity (FC) response pattern to acute pain stimulus in the motor (MC) and prefrontal (PFC) cortex assessed by near-infrared spectroscopy (fNIRS) before and after a cold pressor test utilizing water (0–1 °C). Also, we assessed the relationship between this genotype with the DPMS function and quality of life. We included 42 women (Val/Val = 30; Val/Met = 12) with fibromyalgia, ages 18–65. The MANCOVA comparing Val/Met to Val/Val genotypes showed higher ΔFC between left(l)-PFC—l-MC (β = 0.357, p = 0.048), l-PFC—right(r)-PFC (β = 0.249, p = 0.012), l-PFC—r-MC (β = 0.226, p = 0.022), and l-MC—r-PFC (β = 0.260, p = 0.016). Val/Met genotypes showed higher efficiency of the DPMS and lower disability due to pain. Here we show that fibromyalgia patients carrying the Val/Met BDNF genotype presented an increased ΔFC across MC and PFC in response to acute pain associated with differences in acute pain perception and fibromyalgia symptoms.

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Hyper-connectivity between the left motor cortex and prefrontal cortex is associated with the severity of dysfunction of the descending pain modulatory system in fibromyalgia

Cited by 3 publications

References 76 publications

Editorial: Bench to Bedside – the translation of intracortical inhibition marker to clinical practice

Editorial: Bench to Bedside – the translation of intracortical inhibition marker to clinical practice

Motor cortex inhibition as a fibromyalgia biomarker

Functional connectivity response to acute pain assessed by fNIRS is associated with BDNF genotype in fibromyalgia: an exploratory study

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