Disrupted functional connectivity between the periaqueductal gray and other brain regions in a rat model of recurrent headache

Jia, Zhihua; Tang, Wenjing; Zhao, Delong; Yu, Shengyuan

doi:10.1038/s41598-017-04060-6

Cited by 19 publications

(24 citation statements)

References 62 publications

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“… 46 These data reveal an impairment of the descending pain modulatory circuits in the process of migraine transformation, leading to loss of pain inhibition and hyperexcitability in nociceptive areas. Similar atypical functional connectivity of the PAG with brain regions involved in nociception, somatosensory processing, emotional processing, and pain modulation has been revealed in rats induced by repeated meningeal inflammation, 47 indicating that this brainstem dysfunction may be the consequence of recurring headache attacks. Meanwhile, medication-overuse also aggravates the maladaptation of descending pain-modulation.…”

Section: Pathophysiology Of CMmentioning

confidence: 56%

Chronic migraine: A process of dysmodulation and sensitization

Min

2018

Mol Pain

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104

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Chronic migraine is a common chronic daily headache featured by frequent headache attacks with at least 15 headache days per month, which brings great disease burden to both the sufferers and the society. Transformed from episodic migraine, the pathophysiology of chronic migraine is not fully understood, even though several risk factors have been associated with migraine progression. Recent studies have identified both structural and functional alterations in some brain regions of chronic migraine patients indicating that maladaptation of the top-down pain modulation and subsequent sensitization of trigeminal system may be important in the pathogenesis of chronic migraine. Moreover, biochemical analysis has confirmed several molecules related to chronic migraine, which may serve as biomarkers and potential therapeutic targets. Chronic migraine is undertreated because of its poor treatment response and limited therapy options. In this article, we reviewed the latest data to outline the clinical feature, pathophysiological mechanism, and management of chronic migraine, in the expectation to provide direction for future research and finally to take good care of chronic migraine patients.

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Section: Pathophysiology Of CMmentioning

confidence: 56%

Chronic migraine: A process of dysmodulation and sensitization

Min

2018

Mol Pain

Self Cite

104

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“…The sensory process and modulatory neuromechanisms in repeated migraine attacks with thermal pain threshold have also been reported in CM animal and human models. In a rat model of CM induced by repeated meningeal infusion of inflammatory soup, there were notable changes in functional connectivity (FC) between PAG with PFC, thalamus, and other regions involved in nociception (Jia et al, 2017). In humans, similar changes in FC where found in high frequent episodic migraineurs between PAG and PFC (Solstrand and Dahlberg et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system

Jassar

Nascimento

Kaciroti

et al. 2019

NeuroImage: Clinical

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Objective To evaluate, in vivo , the impact of ongoing chronic migraine (CM) attacks on the endogenous μ-opioid neurotransmission. Background CM is associated with cognitive-emotional dysfunction. CM is commonly associated with frequent acute medication use, including opioids. Methods We scanned 15 migraine patients during the spontaneous headache attack (ictal phase): 7 individuals with CM and 8 with episodic migraine (EM), as well as 7 healthy controls (HC), using positron emission tomography (PET) with the selective μ-opioid receptor (μOR) radiotracer [ 11 C]carfentanil. Migraineurs were scanned in two paradigms, one with thermal pain threshold challenge applied to the site of the headache, and one without thermal challenge. Multivariable analysis was performed between the μ-opioid receptor availability and the clinical data. Results μOR availability, measured with [ 11 C]carfentanil nondisplaceable binding potential (BP ND ), in the left thalamus (P-value = 0.005) and left caudate (P-value = 0.003) were decreased in CM patients with thermal pain threshold during the ictal phase relative to HC. Lower μOR BP ND in the right parahippocampal region (P-value = 0.001) and right amygdala (P-value = 0.002) were seen in CM relative to EM patients. Lower μOR BP ND values indicate either a decrease in μOR concentration or an increase in endogenous μ-opioid release in CM patients. In the right amygdala, 71% of the overall variance in μOR BP ND levels was explained by the type of migraine (CM vs. EM: partial-R 2 = 0.47, P-value<0.001, Cohen's effect size d = 2.6SD), the severity of the attack (pain area and intensity number summation [P.A.I.N.S.]: partial-R 2 = 0.16, P-value = 0.031), and the thermal pain threshold (allodynia: partial-R 2 = 0.08). Conclusions Increased endogenous μ-opioid receptor-mediated neurotransmission is seen in the limbic system of CM patients, especially in right amygdala, which is highly modulated by the attack frequency, pain severity, and sensitivity. This study demonstrates for the first time the negative impact of chronification and exacerbation of headache attacks on the endogenous μ-opioid mechanisms of migraine patients. ClinicalTrials.gov identifier: NCT03004313

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“…26 The MRI data collection were performed as described in our previous research. 24 Briefly, the rats were anesthetized with isoflurane in a gas mixture of 40% O 2 and 60% N 2 . Each rat was placed in the prone position on an MR-compatible stereotactic holder with a bite bar and a gas mask to exhaust the isoflurane.…”

Section: Methodsmentioning

confidence: 99%

Atypical functional connectivity between the anterior cingulate cortex and other brain regions in a rat model of recurrent headache

et al. 2019

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We explored the atypical functional connectivity between the anterior cingulate cortex and other brain areas in rats subjected to repeated meningeal nociception. The rat model was established by infusing an inflammatory soup through supradural catheters in conscious rats. Rats were subdivided according to the frequency of the inflammatory soup infusions. Functional connectivity analysis seeded on the anterior cingulate cortex was performed on rats 21 days after inflammatory soup infusion. Glyceryl trinitrate was injected following baseline scanning in the low-frequency inflammatory soup group and magnetic resonance imaging data were acquired 1 h after the injection. The rats exhibited nociceptive behavior after high-frequency inflammatory soup infusion. The anterior cingulate cortex showed increased functional connectivity with the cerebellum in the inflammatory soup groups. The medulla showed increased functional connectivity with the anterior cingulate cortex in the ictal period in the low-frequency inflammatory soup rats. Several areas showed increased functional connectivity with the anterior cingulate cortex in the high-frequency inflammatory soup group, including the pontine tegmentum, midbrain, thalamus, corpus callosum, hippocampus, and retrosplenial, visual, sensory, and motor cortices. This study indicated that the medulla participates in the early stage of a migraine attack and may be associated with the initiation of migraine. Sensitization of the trigeminal nociceptive pathway might contribute to the cutaneous allodynia seen in chronic migraine. Brain areas important for memory function may be related to the chronification of migraine. Electrophysiological studies should examine those migraine-related areas and provide new targets for migraine treatment and prevention.

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Disrupted functional connectivity between the periaqueductal gray and other brain regions in a rat model of recurrent headache

Cited by 19 publications

References 62 publications

Chronic migraine: A process of dysmodulation and sensitization

Chronic migraine: A process of dysmodulation and sensitization

Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system

Atypical functional connectivity between the anterior cingulate cortex and other brain regions in a rat model of recurrent headache

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