scholarly journals Altered activity in the nucleus raphe magnus underlies cortical hyperexcitability and facilitates trigeminal nociception in a rat model of medication overuse headache

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Prangtip Potewiratnanond ◽  
Supang Maneesri le Grand ◽  
Anan Srikiatkhachorn ◽  
Weera Supronsinchai
Keyword(s):  
Rat Model ◽  
Chronic Exposure ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Neuronal Firing ◽  
Control Group ◽  
Nucleus Raphe Magnus ◽  
Cortical Hyperexcitability ◽  
Trigeminal Nociception ◽  
Raphe Magnus

Abstract Background The pathogenesis of medication overuse headache (MOH) involves hyperexcitability of cortical and trigeminal neurons. Derangement of the brainstem modulating system, especially raphe nuclei may contribute to this hyperexcitability. The present study aimed to investigate the involvement of the nucleus raphe magnus (NRM) in the development of cortical and trigeminal hyperexcitability in a rat model of MOH. Results Chronic treatment with acetaminophen increased the frequency of cortical spreading depression (CSD) and the number of c-Fos-immunoreactive (Fos-IR) neurons in the trigeminal nucleus caudalis (TNC). In the control group, muscimol microinjected into the NRM increased significantly the frequency of CSD-evoked direct current shift and Fos-IR neurons in the TNC. This facilitating effect was not found in rats with chronic acetaminophen exposure. In a model of migraine induced by intravenous systemic infusion of nitroglycerin (NTG), rats with chronic exposure to acetaminophen exhibited significantly more frequent neuronal firing in the TNC and greater Fos-IR than those without the acetaminophen treatment. Muscimol microinjection increased neuronal firing in the TNC in control rats, but not in acetaminophen-treated rats. The number of Fos-IR cells in TNC was not changed significantly. Conclusion Chronic exposure to acetaminophen alters the function of the NRM contributing to cortical hyperexcitability and facilitating trigeminal nociception.

Cortical hyperexcitability and mechanism of medication-overuse headache

Cephalalgia ◽  
2010 ◽  
Vol 30 (9) ◽  
pp. 1101-1109 ◽  
Author(s):  
Weera Supornsilpchai ◽  
Supang Maneesri le Grand ◽  
Anan Srikiatkhachorn
Keyword(s):  
Parietal Cortex ◽  
Spreading Depression ◽  
Medication Overuse ◽  
Cortical Excitability ◽  
Medication Overuse Headache ◽  
Cortical Hyperexcitability ◽  
Trigeminal Nociception ◽  
Daily Dose ◽  
Fos Expression ◽  
Increased Susceptibility

The present study was conducted to determine the effect of acute (1 h) and chronic (daily dose for 30 days) paracetamol administration on the development of cortical spreading depression (CSD), CSD-evoked cortical hyperaemia and CSD-induced Fos expression in cerebral cortex and trigeminal nucleus caudalis (TNC). Paracetamol (200 mg/kg body weight, intraperitonealy) was administered to Wistar rats. CSD was elicited by topical application of solid KCl. Electrocorticogram and cortical blood flow were recorded. Results revealed that acute paracetamol administration substantially decreased the number of Fos-immunoreactive cells in the parietal cortex and TNC without causing change in CSD frequency. On the other hand, chronic paracetamol administration led to an increase in CSD frequency as well as CSD-evoked Fos expression in parietal cortex and TNC, indicating an increase in cortical excitability and facilitation of trigeminal nociception. Alteration of cortical excitability which leads to an increased susceptibility of CSD development can be a possible mechanism underlying medication-overuse headache.

Central Sensitization of The Trigeminal and Somatic Nociceptive Systems in Medication Overuse Headache Mainly Involves Cerebral Supraspinal Structures

Cephalalgia ◽  
2006 ◽  
Vol 26 (9) ◽  
pp. 1106-1114 ◽  
Author(s):  
I Ayzenberg ◽  
M Obermann ◽  
P Nyhuis ◽  
M Gastpar ◽  
V Limmroth ◽  
...  
Keyword(s):  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Blink Reflex ◽  
Episodic Migraine ◽  
Upper Limbs ◽  
Trigeminal Nociception ◽  
Simultaneous Registration ◽  
Nociceptive Blink Reflex ◽  
Before And After ◽  
Stimulation Of

Trigeminal and somatic nociceptive systems were studied in controls ( n = 15), episodic migraine ( n = 16), analgesics ( n = 14) and triptan-induced medication overuse headache (MOH) ( n = 15) before and after withdrawal. Patients with MOH and comorbid depressive symptoms and depression without headache were studied to investigate the influence of depression. Trigeminal nociception was studied by simultaneous registration of pain-related cortical potentials (PREP) and nociceptive blink reflex (nBR) following nociceptive-specific electrical stimulation of the forehead. Somatic nociception was evaluated using PREP of upper limbs. We found facilitation of both trigeminal and somatic PREP but not of nBR in MOH, which normalized after withdrawal. No differences were found comparing analgesics vs. triptan MOH. No differences were observed between controls and patients with episodic migraine and depression without headache. A transient facilitation was found of trigeminal and somatic nociceptive systems in MOH, which was more pronounced on a supraspinal level.

scholarly journals A Multimodal MR Imaging Study of the Effect of Hippocampal Damage on Affective and Cognitive Functions in a Rat Model of Chronic Exposure to a Plateau Environment

2022 ◽  
Author(s):  
Dongyong Zhu ◽  
Bo He ◽  
Mengdi Zhang ◽  
Yixuan Wan ◽  
Ruibin Liu ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Rat Model ◽  
Chronic Exposure ◽  
Imaging Techniques ◽  
Male Rats ◽  
Chemical Exchange Saturation Transfer ◽  
Tibet Plateau ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Hippocampal Damage

AbstractProlonged exposure to high altitudes above 2500 m above sea level (a.s.l.) can cause cognitive and behavioral dysfunctions. Herein, we sought to investigate the effects of chronic exposure to plateau hypoxia on the hippocampus in a rat model by using voxel-based morphometry, creatine chemical exchange saturation transfer (CrCEST) and dynamic contrast-enhanced MR imaging techniques. 58 healthy 4-week-old male rats were randomized into plateau hypoxia rats (H group) as the experimental group and plain rats (P group) as the control group. H group rats were transported from Chengdu (500 m a.s.l.), a city in a plateau located in southwestern China, to the Qinghai–Tibet Plateau (4250 m a.s.l.), Yushu, China, and then fed for 8 months there, while P group rats were fed in Chengdu (500 m a.s.l.), China. After 8 months of exposure to plateau hypoxia, open-field and elevated plus maze tests revealed that the anxiety-like behavior of the H group rats was more serious than that of the P group rats, and the Morris water maze test revealed impaired spatial memory function in the H group rats. Multimodal MR imaging analysis revealed a decreased volume of the regional gray matter, lower CrCEST contrast and higher transport coefficient Ktrans in the hippocampus compared with the P group rats. Further correlation analysis found associations of quantitative MRI parameters of the hippocampus with the behavioral performance of H group rats. In this study, we validated the viability of using noninvasive multimodal MR imaging techniques to evaluate the effects of chronic exposure to a plateau hypoxic environment on the hippocampus.

scholarly journals Sensitization of kappa opioid system in the amygdala in rat model of stress-induced medication overuse headache

2018 ◽  
Vol WCP2018 (0) ◽  
pp. PO3-2-43
Author(s):  
Daigo Ikegami ◽  
Jennifer Y Xie ◽  
Milena De Felice ◽  
Caroline M Kopruszinski ◽  
Megumi Ikegami ◽  
...  
Keyword(s):  
Rat Model ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Opioid System ◽  
Kappa Opioid

scholarly journals Meta-analysis of prednisone in withdrawal therapy following medication overuse headache

2021 ◽  
Vol 26 (4) ◽  
pp. 761-766
Author(s):  
Wenmiao Jie ◽  
Jianzhong Xiong ◽  
Xiaohua Yan
Keyword(s):  
Medication Overuse ◽  
Meta Analysis ◽  
Medication Overuse Headache ◽  
Control Group ◽  
Randomized Control Trials ◽  
Significant Difference ◽  
Withdrawal Therapy ◽  
Randomized Control ◽  
Experimental Group

The objective of this meta-analysis was to evaluate the therapeutic effectiveness of prednisone in withdrawal therapy following medication overuse headache. The Cochrane, PubMed, EMBASE, Web of Science, CNKI, VIP, and Wanfang data were searched to identify randomized control trials of prednisone for the treatment of medication overuse headache. Two researchers independently screened published studies according to inclusion and exclusion criteria, and evaluated the methodological quality of included studies. Revman 5.3 software was used to analyze the extracted data, and a total of six randomized control trials involving 510 patients were included in the study. Meta-analysis indicated that there was no significant difference in the ratio of taking painkillers again after withdrawal (RR=0.89, 95% CI: 0.70,1.14, P=0.36) compared with the control group. There was also no significant difference between the experimental group and the control group in the incidence of withdrawal reactions (RR=1.28, 95% CI: 0.87, 1.89, P=0.21), severity of headache (RR=1.56, 95% CI: -4.83, 7.95, P=0. 63) and the frequency of headache attacks after withdrawal (RR=0.14, 95% CI: -0.35, 0.63, P=0.58). It is concluded that prednisone does not alleviate symptoms in patients with medication overuse headache after withdrawal.

scholarly journals Evaluation of LY573144 (lasmiditan) in a preclinical model of medication overuse headache

Cephalalgia ◽  
2020 ◽  
Vol 40 (9) ◽  
pp. 903-912 ◽  
Author(s):  
Jill C Rau ◽  
Edita Navratilova ◽  
Janice Oyarzo ◽  
Kirk W Johnson ◽  
Sheena K Aurora ◽  
...  
Keyword(s):  
Rat Model ◽  
Acute Treatment ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Light Stress ◽  
Preclinical Model ◽  
Sprague Dawley ◽  
Drug Induced ◽  
No Donor ◽  
Cutaneous Allodynia

Background Medication overuse is a significant issue that complicates the treatment of headache disorders. The most effective medications for the acute treatment of migraine all have the capacity to induce medication overuse headache (MOH). Novel acute migraine-specific treatments are being developed. However, because the mechanism(s) underlying medication overuse headache are not well understood, it is difficult to predict whether any particular acute medication will induce MOH in susceptible individuals. LY573144 (lasmiditan), a 5-HT1F receptor agonist, has recently been shown to be effective in the acute treatment of migraine in phase 3 trials. The aim of this study is to determine whether frequent administration of lasmiditan induces behaviors consistent with MOH in a pre-clinical rat model. Methods Sprague Dawley rats were administered six doses of lasmiditan (10 mg/kg), sumatriptan (10 mg/kg), or sterile water orally over 2 weeks and cutaneous allodynia was evaluated regularly in the periorbital and hindpaw regions using von Frey filaments. Testing continued until mechanosensitivity returned to baseline levels. Rats were then submitted to bright light stress (BLS) or nitric oxide (NO) donor administration and were again evaluated for cutaneous allodynia in the periorbital and hindpaw regions hourly for 5 hours. Results Both lasmiditan and sumatriptan exhibited comparable levels of drug-induced cutaneous allodynia in both the periorbital and hindpaw regions, which resolved after cessation of drug administration. Both lasmiditan and sumatriptan pre-treatment resulted in cutaneous allodynia that was evoked by either BLS or NO donor. Conclusions In a pre-clinical rat model of MOH, oral lasmiditan, like sumatriptan, induced acute transient cutaneous allodynia in the periorbital and hindpaw regions that after resolution could be re-evoked by putative migraine triggers. These results suggest that lasmiditan has the capacity to induce MOH through persistent latent peripheral and central sensitization mechanisms.

scholarly journals Longitudinal assessment of gray matter volumes and white matter integrity in patients with medication-overuse headache

2018 ◽  
Vol 31 (2) ◽  
pp. 150-156 ◽  
Author(s):  
Yesim Beckmann ◽  
Sevgin Gökçe ◽  
Nabi Zorlu ◽  
H Sabiha Türe ◽  
Fazıl Gelal
Keyword(s):  
White Matter ◽  
Gray Matter ◽  
Drug Withdrawal ◽  
Medication Overuse ◽  
Diffusion Tensor ◽  
Smoking Status ◽  
Medication Overuse Headache ◽  
White Matter Integrity ◽  
Control Group ◽  
The Brain

Background Medication-overuse headache is a common clinical entity, but neuroimaging studies investigating volumetric and microstructural alterations of the brain in medication-overuse headache are rare. Therefore, in the current longitidunal study we evaluated gray matter volume and white matter integrity in patients with medication-overuse headache before and after drug withdrawal. Methods A prospective study evaluated 27 patients with medication-overuse headache and 27 age-, sex-, and education-matched healthy adults. High-resolution T1-weighted magnetic resonance imaging and diffusion tensor imaging were obtained from the control group and medication-overuse headache patients before and six months after drug withdrawal. Tract-based spatial statistics of multiple diffusivity indices and voxel-based morphometry were employed to investigate white and gray matter abnormalities. Results No correlation was found between age, gender, education and smoking status in both groups. The most commonly overused medications were simple analgesics (96.3%) and combined analgesics (3.7%). The mean duration of the history of medication overuse and headaches was 56.7 ± 63.5 months. White matter diffusional and gray matter morphological alterations including volume, fractional anisotropy, radial diffusivity, and axial diffusivity analyses showed no significant relationship in the patients before and six months after withdrawal of analgesics. Also no difference was observed between the patients versus controls. Conclusion Our data demonstrated no structural alterations within the brain in medication-overuse headache.

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