Drug-induced changes in cortical inhibition in medication overuse headache

Cephalalgia ◽  
2011 ◽  
Vol 31 (12) ◽  
pp. 1282-1290 ◽  
Author(s):  
Antonio Currà ◽  
Gianluca Coppola ◽  
Manuela Gorini ◽  
Elisa Porretta ◽  
Martina Bracaglia ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Primary Motor Cortex ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Silent Period ◽  
Cortical Inhibition ◽  
Drug Induced ◽  
Normal Limits ◽  
Inhibitory Mechanisms ◽  
Episodic Migraineurs

Background: We investigated whether chronic headache related to medication overuse (MOH) is associated with changes in brain mechanisms regulating inhibitory cortical responses compared with healthy volunteers and episodic migraineurs recorded between attacks, and whether these changes differ according to the drug overused. Subjects and Methods: We studied 40 MOH patients whose symptoms were related to triptans alone, non-steroidal anti-inflammatory drugs (NSAIDs) or both medications combined, 12 migraineurs and 13 healthy volunteers. We used high-intensity transcranial magnetic stimulation over the primary motor cortex to assess the silent period from contracted perioral muscles. Results: In MOH patients the cortical silent period differed according to the type of headache medication overused: in patients overusing triptans alone it was shorter than in healthy volunteers (44.7 ± 14.2 vs. 108.1 ± 30.1 ms), but similar to that reported in migraineurs (59.9 ± 30.4 ms), whereas in patients overusing NSAIDs alone or triptans and NSAIDs combined duration of silent period was within normal limits (80.6 ± 46.4 and 103.8 ± 47.2 ms). Conclusions: Compared with episodic migraineurs, MOH patients overusing triptans have no significant change in cortical inhibition, whereas those overusing NSAIDs have an increase in cortical inhibitory mechanisms. We attribute these changes to medication-induced neural adaptation promoted by changes in central serotonin neurotransmission.

scholarly journals Validation of potential candidate biomarkers of drug-induced nephrotoxicity and allodynia in medication-overuse headache

2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Elisa Bellei ◽  
Emanuela Monari ◽  
Stefania Bergamini ◽  
Aurora Cuoghi ◽  
Aldo Tomasi ◽  
...  
Keyword(s):  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Potential Candidate ◽  
Drug Induced

scholarly journals Increased cerebral responses to salient transitions between alternating stimuli in chronic migraine with medication overuse headache and during migraine attacks

Cephalalgia ◽  
2019 ◽  
Vol 39 (8) ◽  
pp. 988-999 ◽  
Author(s):  
Volodymyr B Bogdanov ◽  
Olena V Bogdanova ◽  
Alessandro Viganò ◽  
Quentin Noirhomme ◽  
Steven Laureys ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Chronic Migraine ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Blood Oxygenation Level Dependent ◽  
Pain Modulation ◽  
Blood Oxygenation ◽  
Blood Oxygenation Level ◽  
Oxygenation Level ◽  
Headache Patients

Introduction In a previous study exploring central pain modulation with heterotopic stimuli in healthy volunteers, we found that transitions between sustained noxious and innocuous thermal stimulations on the foot activated the “salience matrix”. Knowing that central sensory processing is abnormal in migraine, we searched in the present study for possible abnormalities of these salient transitional responses in different forms of migraine and at different time points of the migraine cycle. Methods Participants of both sexes, mostly females, took part in a conditioned pain modulation experiment: Migraineurs between (n = 14) and during attacks (n = 5), chronic migraine patients with medication overuse headache (n = 7) and healthy volunteers (n = 24). To evoke the salience response, continuous noxious cold or innocuous warm stimulations were alternatively applied on the right foot. Cerebral blood oxygenation level dependent responses were recorded with fMRI. Results Switching between the two stimulations caused a significant transition response in the “salience matrix” in all subject groups (effect of the condition). Moreover, some group effects appeared on subsequent post-hoc analyses. Augmented transitional blood oxygenation level dependent responses in the motor cortex and superior temporal sulcus were found in two patient groups compared to healthy controls: chronic migraine with medication overuse headache patients and migraineurs recorded during an attack. In chronic migraine with medication overuse headache patients, salience-related responses were moreover greater in the premotor cortex, supplementary motor area, lingual gyrus and dorso-medial prefrontal cortex and other “salience matrix” areas, such as the anterior cingulate and primary somatosensory cortices. Conclusion This study shows salience-related hyperactivation of affective and motor control areas in chronic migraine with medication overuse headache patients and, to a lesser extent, in episodic migraine patients during an attack. The greater extension of exaggerated blood oxygenation level dependent responses to unspecific salient stimuli in chronic migraine with medication overuse headache than during a migraine attack could be relevant for headache chronification.

scholarly journals Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache

2013 ◽  
Vol 14 (1) ◽  
Author(s):  
Elisa Bellei ◽  
Emanuela Monari ◽  
Aurora Cuoghi ◽  
Stefania Bergamini ◽  
Simona Guerzoni ◽  
...  
Keyword(s):  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Drug Induced ◽  
Early Biomarkers ◽  
Proteomic Approach

Medication overuse headache

Neurology ◽  
2017 ◽  
Vol 89 (12) ◽  
pp. 1296-1304 ◽  
Author(s):  
Ann I. Scher ◽  
Paul B. Rizzoli ◽  
Elizabeth W. Loder
Keyword(s):  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Secondary Headache ◽  
Headache Frequency ◽  
Drug Induced ◽  
Strong Basis ◽  
Medication Withdrawal ◽  
Symptomatic Medication ◽  
Treatment Limitation ◽  
Drug Induced Headache

It is a widely accepted idea that medications taken to relieve acute headache pain can paradoxically worsen headache if used too often. This type of secondary headache is referred to as medication overuse headache (MOH); previously used terms include rebound headache and drug-induced headache. In the absence of consensus about the duration of use, amount, and type of medication needed to cause MOH, the default position is conservative. A common recommendation is to limit treatment to no more than 10 or 15 days per month (depending on medication type) to prevent headache frequency progression. Medication withdrawal is often recommended as a first step in treatment of patients with very frequent headaches. Existing evidence, however, does not provide a strong basis for such causal claims about the relationship between medication use and frequent headache. Observational studies linking treatment patterns with headache frequency are by their nature confounded by indication. Medication withdrawal studies have mostly been uncontrolled and often have high dropout rates. Evaluation of this evidence suggests that only a minority of patients required to limit the use of symptomatic medication may benefit from treatment limitation. Similarly, only a minority of patients deemed to be overusing medications may benefit from withdrawal. These findings raise serious questions about the value of withholding or withdrawing symptom-relieving medications from people with frequent headaches solely to prevent or treat MOH. The benefits of doing so are smaller, and the harms larger, than currently recognized. The concept of MOH should be viewed with more skepticism. Until the evidence is better, we should avoid dogmatism about the use of symptomatic medication. Frequent use of symptom-relieving headache medications should be viewed more neutrally, as an indicator of poorly controlled headaches, and not invariably a cause.

scholarly journals Medication Overuse Headache: A Trap for the Headache Patients

2013 ◽  
Vol 3 (2) ◽  
pp. 94-98
Author(s):  
A Rahman ◽  
R Habib ◽  
NB Bhowmik ◽  
A Haque
Keyword(s):  
Chronic Daily Headache ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Primary Headache ◽  
Headache Disorder ◽  
Tension Type Headache ◽  
Clinical Impression ◽  
Drug Induced ◽  
Daily Headache ◽  
Drug Induced Headache

Medication Overuse Headache (MOH) was previously termed analgesic rebound headache, drug-induced headache, and medication-misuse headache. It is not a primary headache but frequently coexists with primary chronic daily headache. All acute symptomatic medications used to treat headaches have the potential for causing MOH. Highest with opioids, butalbital-containing combination analgesics, and aspirin/ acetaminophen/caffeine combinations. The development is typically preceded by an episodic headache disorder, usually migraine or tension-type headache, that has been treated with frequent and excessive amounts of acute symptomatic medications. The diagnosis is based upon clinical impression. A history of analgesic use averaging more than two to three days per week in association with chronic daily headache is suggestive. The diagnosis is made when the pattern of frequent headaches fulfills the diagnostic criteria for MOH. The basic steps in the management: Patient education, withdrawal of the offending medication, bridge (transitional) therapy, establishment of a headache treatment regimen covering acute and preventive care, follow up and relapse prevention. Birdem Med J 2013; 3(2): 94-98 DOI: http://dx.doi.org/10.3329/birdem.v3i2.17213

Cortical silent period

2021 ◽  
Author(s):  
Markus Kofler ◽  
Ulf Ziemann ◽  
Vasilios K. Kimiskidis
Keyword(s):  
Primary Motor Cortex ◽  
Silent Period ◽  
Clinical Applications ◽  
Emg Activity ◽  
Cortical Silent Period ◽  
Physiological Basis ◽  
Inhibitory Mechanisms ◽  
Magnetic Stimulus ◽  
Health And Disease ◽  
Voluntary Muscle Contraction

The cortical silent period (cSP) refers to a period of suppression or silencing of ongoing electromyographic (EMG) activity during voluntary muscle contraction induced by a magnetic stimulus over the contralateral primary motor cortex. This chapter summarizes the physiological basis of the cSP, discusses technical aspects and recommendations on how to record and analyze it, and provides an overview of useful clinical applications. Evidence is presented that multiple spinal mechanisms are implicated in the initial part of the cSP, but some may be also active further on, whereas long-lasting cortical inhibitory mechanisms operate throughout the entire cSP, with an emphasis during its later part. The cSP is a highly relevant and clinically useful tool to assess inhibitory corticomotoneuronal mechanisms in health and disease.

scholarly journals Pain perception is altered in patients with medication-overuse headache but can improve after detoxification

2012 ◽  
Vol 3 (3) ◽  
pp. 198-198
Author(s):  
Signe Bruun Munksgaard ◽  
Lars Bendtsen ◽  
Rigmor Højland Jensen
Keyword(s):  
Healthy Volunteers ◽  
Central Sensitization ◽  
Pain Perception ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Primary Headaches ◽  
Pain Thresholds ◽  
Pressure Pain ◽  
Pressure Pain Thresholds

Abstract Background Previously, central sensitization has been found in chronic, primary headaches but pain perception in MOH patients has only scarcely been studied. Aim To investigate pain perception before and during detoxification in patients with medication overuse headache (MOH). Methods 35 patients with MOH following structured detoxification programmes were tested before and 2, 6 and 12 months after withdrawal and 40 age and sex matched, healthy volunteers were tested for comparison. We measured cephalic and extra cephalic pressure pain thresholds (PPT) and supra-threshold pressure pain (STPP) as well as extra cephalic pain thresholds, supra-threshold pain and wind-up for electrical stimulation. Results At baseline, cephalic and extra cephalic PPTs were significantly lower in patients with MOH compared with healthy volunteers. Cephalic STPP was significantly higher in MOH patients compared with healthy volunteers but decreased significantly from baseline to the 6-month and 12-month follow-up. Supra-threshold pain for a single electrical stimulus was significantly higher in MOH patients compared with healthy volunteers. In contrast to healthy volunteers, patients with MOH did not exhibit wind-up before withdrawal. After 2 months, MOH patients had regained ability to wind-up and this persisted at 6-month and 12-month follow-up. Conclusions Patients with MOH have altered pain sensation and exhibit both allodynia and hyperalgesia indicating central sensitization. Withdrawal from medication overuse causes significant decrease in central sensitization. The ability to wind-up is altered in MOH patients, probably as a consequence of medication overuse, but it can be regained after withdrawal. These findings emphasize the need for detoxification in MOH.

scholarly journals Competition, Conflict and Change of Mind: A Role of GABAergic Inhibition in the Primary Motor Cortex

2022 ◽  
Vol 15 ◽  
Author(s):  
Bastien Ribot ◽  
Aymar de Rugy ◽  
Nicolas Langbour ◽  
Anne Duron ◽  
Michel Goillandeau ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Silent Period ◽  
Single Pulse ◽  
Electromyographic Activity ◽  
Continuous Control ◽  
Gabaergic Inhibition ◽  
Inhibitory Mechanisms ◽  
Post Onset

Deciding between different voluntary movements implies a continuous control of the competition between potential actions. Many theories postulate a leading role of prefrontal cortices in this executive function, but strong evidence exists that a motor region like the primary motor cortex (M1) is also involved, possibly via inhibitory mechanisms. This was already shown during the pre-movement decision period, but not after movement onset. For this pilot experiment we designed a new task compatible with the dynamics of post-onset control to study the silent period (SP) duration, a pause in electromyographic activity after single-pulse transcranial magnetic stimulation that reflects inhibitory mechanisms. A careful analysis of the SP during the ongoing movement indicates a gradual increase in inhibitory mechanisms with the level of competition, consistent with an increase in mutual inhibition between alternative movement options. However, we also observed a decreased SP duration for high-competition trials associated with change-of-mind inflections in their trajectories. Our results suggest a new post-onset adaptive process that consists in a transient reduction of GABAergic inhibition within M1 for highly conflicting situations. We propose that this reduced inhibition softens the competition between concurrent motor options, thereby favoring response vacillation, an adaptive strategy that proved successful at improving behavioral performance.

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.

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