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Illustrative traces of somatosensory evoked potentials habituation in a healthy volunteer, MO Interictally and ictally, and MOH patient.
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Medication-overuse headache (MOH) is a frequent, disabling disorder. Despite a controversial pathophysiology convincing evidence attributes a pivotal role to central sensitization. Most patients with MOH initially have episodic migraine without aura (MOA) characterized interictally by an absent amplitude decrease in cortical evoked potentials to re...
Contexts in source publication
Context 1
... the 300 evoked responses were partitioned in 3 sequential blocks of 100 responses ( Figure 1). Each block was averaged off-line ("block averages") and ana- lyzed for N20-P25 amplitudes. ...Context 2
... SEP recordings were obtained from all patients and controls participating in the study (Figure 1). On grand average SEP recordings after electrical median nerve stimulation latencies of N13, N20, P25 and N33 compo- nents were not different between groups (for each measure F(3,131), p > 0.05) whereas their amplitudes significantly differed between groups (F(3,131) = 2.75, p = 0.045). ...Similar publications
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Citations
... Electrophysiological investigations have shown neuronal hyperexcitability with an increased stimulation response and a habituation deficit in patients with medication overuse headaches. These alterations have been observed with different stimulation techniques, such as somatosensory-evoked potentials [41,42], cold pressor tests [43], and laser CO 2 evoked potentials [44], both in the cephalic and extracephalic regions [41]. Additionally, the hyperexcitability pattern in MOH seems to depend on the overused drug. ...
... Additionally, the hyperexcitability pattern in MOH seems to depend on the overused drug. Patients with this condition show an increased amplitude of somatosensory-evoked potentials when stimulating the median-nerve, but patients who overuse triptans show lower amplitudes than patients overusing NSAIDs [42]. The observed differences could reflect triptan-induced changes within the central serotonergic transmission. ...
Chronic migraine is a disease with a high burden on patients from both a working and quality of life point of view. The pathophysiology of this subtype of migraine is due to several factors, such as medication overuse. Nevertheless, the detrimental recurring of headache attacks with central and peripheral sensitization plays a central role and explains some additional symptoms complained about by these patients even in the interictal phase. OnabotulinumtoxinA is a therapy indicated for chronic migraine since it has proven to reduce peripheral sensitization, showing even efficacy on central symptoms. The aim of this narrative review is to present the current evidence regarding the effect of OnabotulinumtoxinA on sensitization and interictal symptoms.
... Our main interest was in the rTMS-QPI protocol because we postulated that it might have a therapeutic effect in CM-MOH patients by mitigating the sensitization of their visual cortex [16,42]. Since rTMS-QPI induced in HS electrophysiological indices of a robust inhibition of the visual cortex, we tested this protocol, as a proof-of-concept, in CM-MOH patients who are notoriously difficult to treat [2]. ...
In chronic migraine with medication overuse (CM-MOH), sensitization of visual cortices is reflected by (i) increased amplitude of stimulus-evoked responses and (ii) habituation deficit during repetitive stimulation. Both abnormalities might be mitigated by inhibitory transcranial neurostimulation. Here, we tested an inhibitory quadripulse repetitive transcranial magnetic stimulation (rTMS-QPI) protocol to decrease durably visual cortex excitability in healthy subjects (HS) and explored its therapeutic potential in CM-MOH patients. Pattern-reversal visual evoked potentials (VEP) were used as biomarkers of effect and recorded before (T1), immediately after (T2), and 3 h after stimulation (T3). In HS, rTMS-QPI durably decreased the VEP 1st block amplitude (p < 0.05) and its habituation (p < 0.05). These changes were more pronounced for the P1N2 component that was modified already at T2 up to T3, while for N1P1 they were significant only at T3. An excitatory stimulation protocol (rTMS-QPE) tended to have an opposite effect, restricted to P1N2. In 12 CM-MOH patients, during a four-week treatment (2 sessions/week), rTMS-QPI significantly reduced monthly headache days (p < 0.01). In patients reversing from CM-MOH to episodic migraine (n = 6), VEP habituation significantly improved after treatment (p = 0.005). rTMS-QPI durably decreases visual cortex responsivity in healthy subjects. In a proof-of-concept study of CM-MOH patients, rTMS-QPI also has beneficial clinical and electrophysiological effects, but sham-controlled trials are needed.
... The hyperexcitability pattern in medication overuse headaches appears to depend on the specific overused drug. For instance, patients overusing triptans exhibit lower amplitudes in somatosensory-evoked potentials compared to those overusing NSAIDs [29], potentially reflecting triptan-induced changes in central serotoninergic transmission. ...
Medication overuse headaches are a frequent phenomenon observed in individuals suffering from chronic headaches. It arises due to the excessive consumption of pain-relief medications, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a retrospective study and analyzed the medical records of children and adolescents who were evaluated at the outpatient pediatric headache clinic at the Bnai Zion Medical Center for headaches during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients experiencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with migraine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with the undifferentiated headache of childhood, with the majority (73%) being female. In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pediatric cases, shedding light on its distinct characteristics in the realm of childhood headache disorders. Further research is warranted to elucidate the underlying factors contributing to the observed gender disparity and the distinct prevalence rates among different headache subtypes.
... Pain adaptation was associated with neural activity in the premotor, motor, and somatosensory cortices, such that habituation was associated with reduced activity over time. Reduced sensorydiscriminative processing facilitating lower pain is well documented [33,41] and this process appears to be disrupted in chronic pain patients [17,43]. Using a similar design, it has been reported that stimulation over 8 separate days was associated with reduced BOLD responses to nociceptive stimuli in SII, as well as in the insula, thalamus and putamen [8]. ...
Acute pain serves to warn an organism of potential damage. When nociceptive stimulation persists, two possible responses emerge: If no risk of harm is anticipated, habituation may occur. If harm is considered possible, pain sensitization is likely. An individuals adaptation to prolonged pain may provide insight into their ability to manage resources, and possibly their likelihood of developing chronic pain. Yet, little is known about the stability of these individual differences or their underlying neural mechanisms. Eighty-five participants undertook a repetitive noxious stimulation task and a resting-state scan in an MRI scanner, in a first session. They then completed the same task outside the scanner on three separate days. Pain adaptation was operationalized as the slope of change in pain ratings within session. Intraclass correlations were calculated between slopes across the four sessions, which demonstrated high stability and association with emotional disposition. Individuals who habituated to repeated stimuli showed increasing activity in the anterior hippocampus and amygdala, while individuals who sensitized showed increasing activity in the sensorimotor cortices. These clusters were then used as seeds in resting state analysis, with habituation associated with higher functional connectivity between hippocampus/amygdala and ventromedial prefrontal cortex(vmPFC), and higher connectivity between sensorimotor regions and the hippocampus, amygdala and insula cortex. Our findings suggest that pain adaptation is a stable phenotypic trait, which may have implications for the prediction of chronic pain.
This study implicates neural sensory and appraisal systems in these stable responses, offering insight into the mechanisms underlying trait-like responses to prolonged nociceptive input.
... In addition to factors related to previous headache, psychological factors, personality traits, and a genetic predisposition play important roles (26; 27) (Figure1). Genes involved in complex processes of endogenous pain modulation, drug metabolism, and the serotonin and dopamine systems have been linked to the development of MOH (28). Excessive use of analgesics leads to facilitation of supraspinal pain transmission (29) (Figure 2). ...
Purpose of review: Medication overuse headache (MOH) is an important problem worlwide areas of different controversy regarding its entity. This article reviews the risk factors, comorbidities, pathophysiology, clinical presentation, effective management and prognosis of MOH, by summaries and integrates the results and finding in previously performed more than 15000 studies (from the year of 2010 to 2023) available from the scientific database of the University Medical Library in the University Clinical centre of Niš, which aimed to investigate and define a complexcity of this type of headache. Recent finding: It has been proposed that all acute migraine medications can lead to MOH, with differences in the propensity of different agents to cause the problem. Early data suggests that triptans and other pain killers used for the acute treatment of migraine, may be an exception. Recent studies show that practicioners and the general public are still largely unaware of the problem of medication overuse and its damaging effects. Summary: Although it is likely that MOH does occur and restricting the amount of acute medications is necessary to prevent it. It is also possible that increasing amounts of acute medications are simply a reflection of poorly controlled headaches, rather than a couse. Further researches need to be developed to identify more precisious mechanism in MOH effecitive management and its evolution. Key word: medication overuse headache (MOH)
... In addition to factors related to previous headache, psychological factors, personality traits, and a genetic predisposition play important roles (26; 27) (Figure1). Genes involved in complex processes of endogenous pain modulation, drug metabolism, and the serotonin and dopamine systems have been linked to the development of MOH (28). Excessive use of analgesics leads to facilitation of supraspinal pain transmission (29) (Figure 2). ...
Purpose of review: Medication overuse headache (MOH) is an important problem worlwide areas of different controversy regarding its entity. This article reviews the risk factors, comorbidities, pathophysiology, clinical presentation, effective management and prognosis of MOH, by summaries and integrates the results and finding in previously performed more than 15000 studies (from the year of 2010 to 2023) available from the scientific database of the University Medical Library in the University Clinical centre of Niš, which aimed to investigate and define a complexcity of this type of headache. Recent finding: It has been proposed that all acute migraine medications can lead to MOH, with differences in the propensity of different agents to cause the problem. Early data suggests that triptans and other pain killers used for the acute treatment of migraine, may be an exception. Recent studies show that practicioners and the general public are still largely unaware of the problem of medication overuse and its damaging effects. Summary: Although it is likely that MOH does occur and restricting the amount of acute medications is necessary to prevent it. It is also possible that increasing amounts of acute medications are simply a reflection of poorly controlled headaches, rather than a couse. Further researches need to be developed to identify more precisious mechanism in MOH effecitive management and its evolution.
... The hyperexcitability pattern in medication overuse headaches appears to depend on the specific overused drug. For instance, patients overusing triptans exhibit lower amplitudes in somatosensory evoked potentials compared to those overusing NSAIDs [29], potentially reflecting triptan-induced changes in central serotoninergic transmission. ...
Medication overuse headaches is a frequent phenomenon observed in individuals suf-fering from chronic headaches. It arises due to the excessive consumption of pain-relief medica-tions, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a ret-rospective study by and analyzed the medical records of children and adolescents who were evaluated at outpatient pediatric headache clinic at the Bnai Zion medical center for headache during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients expe-riencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with mi-graine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with undifferentiated headache of childhood, with the majority (73%) being female.In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers, and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pedi-atric cases, shedding light on its distinct characteristics in the realm of childhood headache disor-ders. Further research is warranted to elucidate the underlying factors contributing to the ob-served gender disparity and the distinct prevalence rates among different headache subtypes.
... The rationale behind this matching is that habituation differs based on migraine frequency, being normal in chronic phenotype, similar to ictal EM recordings so that CM has been defined as a "never-ending attack" (18-20). Moreover, patients with MOH show a different electrophysiological pattern from that underlying EM (i.e., initial amplitude increase of VEP, with subsequent lack of habituation) (21). Importantly, despite a mixed cohort, in our study, both groups presented impaired habituation, probably driven by the EM phenotype. ...
Objectives
Migraine is one of the most frequent clinical manifestations of hypermobile Ehlers-Danlos syndrome (hEDS). The comorbidity between these two diseases has been only partially investigated. We aimed to observe whether neurophysiological alterations described in migraineurs in visual evoked potentials (VEPs) were present in hEDS patients with migraine.
Methods
We enrolled 22 hEDS patients with migraine (hEDS) and 22 non-hEDS patients with migraine (MIG), with and without aura (according to ICHD-3), as well as 22 healthy controls (HC). Repetitive pattern reversal (PR)-VEPs were recorded in basal conditions in all participants. During uninterrupted stimulation, 250 cortical responses were recorded (4,000 Hz sample rate) and divided into epochs of 300 ms after the stimulus. Cerebral responses were divided into five blocks. The habituation was calculated as the slope interpolating the amplitudes in each block, for both the N75-P100 and P100-N145 components of PR-VEP.
Results
We observed a significant habituation deficit of the P100-N145 component of PR-VEP in hEDS compared to HC (p = 0.002), unexpectedly more pronounced than in MIG. We observed only a slight habituation deficit of N75-P100 in hEDS, with a slope degree that was intermediate between MIG and HC.
Discussion
hEDS patients with migraine presented an interictal habituation deficit of both VEPs components like MIG. Pathophysiological aspects underlying the pathology could account for the peculiar pattern of habituation in hEDS patients with migraine characterized by a pronounced habituation deficit in the P100-N145 component and a less clear-cut habituation deficit in the N75-P100 component with respect to MIG.
... Withdrawal from overuse drugs reduces the facilitation of pain-related cortical potentials in the trigeminal region 151 . In addition, patients with MOH showed abnormal cortical responses to somatosensory stimulation and lacked the habituation phenomenon 152 . ...
Medication overuse headache (MOH) is a secondary headache disorder attributed to overuse of acute headache medications by a person with an underlying headache disorder, usually migraine or tension-type headache. MOH is common among individuals with 15 or more headache days per month. Although MOH is associated with substantial disability and reductions in quality of life, this condition is often under-recognized. As MOH is both preventable and treatable, it warrants greater attention and awareness. The diagnosis of MOH is based on the history and an unremarkable neurological examination, and is made according to the diagnostic criteria of the International Classification of Headache Disorders third edition (ICHD-3). Pathophysiological mechanisms of MOH include altered descending pain modulation, central sensitization and biobehavioural factors. Treatment of MOH includes the use of headache preventive therapies, but essential to success is eliminating the cause, by reducing the frequency of use of acute headache medication, and perhaps withdrawing the overused medication altogether. Appropriate treatment is usually highly effective, leading to reduced headache burden and acute medication consumption. Medication overuse headache is a secondary headache disorder that occurs in those with a primary headache disorder (commonly tension-type headache or migraine). This Primer reviews the epidemiology, pathophysiology, diagnosis and treatment of medication overuse headache, and discusses how this disorder affects the quality of life of patients.
... The stimulus intensity was set at 1.2 times the motor threshold and the repetition rate at 4.4 Hz. The active recording electrodes were placed over the contralateral parietal area (C3 , 2 cm posterior to C3 in the International 10-20 system), on the fifth cervical spinous process (Cv5), both referenced to Fz, and on the Erb's point on the stimulated side, referenced to the contralateral Erb's point; the ground electrode was placed on the right arm [63]. ...
(1) Background: OnabotulinumtoxinA (BoNT-A) is a commonly used prophylactic treatment for chronic migraine (CM). Although randomized placebo studies have shown its clinical efficacy, the mechanisms by which it exerts its therapeutic effect are still incompletely understood and debated. (2) Methods: We studied in 15 CM patients the cephalic and extracephalic nociceptive and lemniscal sensory systems using electrophysiological techniques before and 1 and 3 months after one session of pericranial BoNT-A injections according to the PREEMPT protocol. We recorded the nociceptive blink reflex (nBR), the trigemino-cervical reflex (nTCR), the pain-related cortical evoked potential (PREP), and the upper limb somatosensory evoked potential (SSEP). (3) Results: Three months after a single session of prophylactic therapy with BoNT-A in CM patients, we found (a) an increase in the homolateral and contralateral nBR AUC, (b) an enhancement of the contralateral nBR AUC habituation slope and the nTCR habituation slope, (c) a decrease in PREP N-P 1st and 2nd amplitude block, and (d) no effect on SSEPs. (4) Conclusions: Our study provides electrophysiological evidence for the ability of a single session of BoNT-A injections to exert a neuromodulatory effect at the level of trigeminal system through a reduction in input from meningeal and other trigeminovascular nociceptors. Moreover, by reducing activity in cortical pain processing areas, BoNT-A restores normal functioning of the descending pain modulation systems.
