Central Sensitization in Migraine: A Narrative Review

Suzuki, Keisuke; Suzuki, Shigeaki; Shiina, Tomohiko; Kobayashi, Saro; Hirata, Koichi

doi:10.2147/jpr.s329280

Cited by 31 publications

(21 citation statements)

References 78 publications

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“…It can be speculated that central processes also play a relevant role in the balance dysfunction of patients with chronic pain. These current results support this statement by demonstrating an association between balance control and central sensitization symptoms, when the latter is considered a determining factor for the risk and perpetuation of chronic pain (Suzuki et al., 2022).…”

Section: Discussionsupporting

confidence: 86%

“…According to the International Association for Study of Pain (IASP), central sensitization is defined as an augmented nociceptive responsiveness of central nervous system (CNS) neurons in the face of normal or subthreshold afferent input (International Association for the Study of Pain (IASP), 2011). In migraine, the presence of central sensitization can be observed through a range of symptoms, which mostly encompass the presence of cutaneous allodynia, primary and secondary hyperalgesia (Suzuki et al., 2022). The presence of cutaneous allodynia is related to an increased risk of migraine chronification (Bigal et al., 2008), and it is present in up to 63% of patients during attacks (Lipton et al., 2008), also often occurring between migraine episodes (Schwedt et al., 2011).…”

Section: Introductionmentioning

confidence: 99%

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Association between central sensitization, pain sensitivity and balance control in patients with migraine

Sennholz,

Szikszay,

Marusich

et al. 2023

European Journal of Pain

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BackgroundBalance alterations are prevalent among pain conditions, including migraine. The mechanisms explaining the association between pain and balance are unclear, as well as whether levels of pain sensitivity correlate with impaired balance. Our aim was therefore to investigate the association between balance, central sensitization symptoms and pain sensitivity in patients with migraine.MethodsThis cross‐sectional study included 50 patients and demographic, clinical information, central sensitization inventory (CSI) and pain catastrophizing (PCS) scores were obtained. Patients underwent a standardized protocol evaluating balance and pain thresholds for cold (CPT), heat (HPT), mechanical (MPT) and pressure (PPT) in trigeminal (V1) and extra‐trigeminal (C6) dermatomes. Data were analysed using Person's correlation, linear regression models and contrasting the presence and absence of central sensitization symptoms through T‐tests.ResultsMild‐to‐moderate correlations were observed between balance and MPT in V1 (r = −0.24, p = 0.046) and C6 (r = −0.41, p = 0.002), CPT in V1 (r = 0.31, p = 0.026), CSI scores (r = 0.27, p = 0.029) and migraine frequency (r = 0.25, p = 0.040). Balance was explained by CPT and MPT (R2 = 0.32, p = 0.001). The variance of CSI was explained by PCS scores and balance (R2 = 0.28, p = 0.001). Patients with symptoms of central sensitization presented an increased balance impairment (p = 0.044) and higher catastrophizing levels (p = 0.001) in contrast to patients without symptoms.ConclusionBalance impairment is associated with reduced pain thresholds and higher CSI scores. These results may help to elucidate the aetiology of balance alterations among chronic pain conditions.SignificanceFor the first time, it has been shown that balance alterations can reflect greater pain sensitivity and signs of central sensitization in patients with migraine. This opens up perspectives for future studies to understand the mechanisms and further factors associated with balance and pain sensitivity in migraine.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Association between central sensitization, pain sensitivity and balance control in patients with migraine

Sennholz,

Szikszay,

Marusich

et al. 2023

European Journal of Pain

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“…Therefore, while loss of efficacy due to some form of drug tolerance during overuse may be one factor (6,7), another factor seems to be headache frequency itself. This could suggest that pathophysiological factors linked to headache frequency, such as increasing and persisting sensitization (26), may also reduce the efficacy of acute medication. Alternatively, or additionally, co-factors such as depression or anxiety may influence both headache frequency and acute medication efficacy ratings.…”

Section: Discussionmentioning

confidence: 99%

What do patients’ efficacy and tolerability ratings of acute migraine medication tell us? Cross-sectional data from the DMKG Headache Registry

et al. 2023

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Background Most migraine patients need an effective acute medication. Real-world data can provide important information on the performance of acute migraine medication in clinical practice. Methods We used data from the German Migraine and Headache Society Headache Registry, where patients rate efficacy and tolerability of and satisfaction with each of their acute headache medications. Results A total of 1756 adult migraine patients (females: 85%, age: 39.5 ± 12.8 years, headache days per month: 13.5 ± 8.1) were included. Of these, 93% used acute medication, most frequently triptans (59.3%) and/or non-opioid analgesics (56.4%), and 58.5% rated efficacy as good or very good. This was more frequent for triptans (75.4%) than for non-opioid analgesics (43.6%, p < 0.001). Among non-opioid analgesics, naproxen was rated most effective (61.9% very good or good, p < 0.001 compared to ibuprofen, acetylsalicylic acid and paracetamol). Patient-rated efficacy significantly declined with higher headache frequencies (p < 0.001), and this effect remained significant after omitting patients overusing acute medication. Conclusion In the present population recruited at specialized headache centers, patients rated triptans as more effective than non-opioid analgesics, naproxen as more effective than ibuprofen, and acute medication efficacy decreased with increasing headache frequency. Trial registration: The German Migraine and Headache Society Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081).

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“…In addition to CGRP, vasoactive intestinal peptide and other neuroinflammatory markers have displayed similar outcomes (92,93). Central sensitization emerges as a subsequent development following prolonged inflammation, often triggered by the activation of second and third-order neurons (94). Glutamate receptors (AMPA and NMDA) are assumed to play a significant role in central sensitization (95).…”

Section: Repetitive and Prolonged Nociception In The Activation Of As...mentioning

confidence: 99%

Medication “underuse” headache

Rattanawong,

Rapoport,

Srikiatkhachorn

2024

Cephalalgia

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Background Many risk factors have been associated with migraine progression, including insufficient and ineffective utilization of migraine medications; however, they have been inadequately explored. This has resulted in suboptimal usage of medications without effective altering of prescribing recommendations for patients, posing a risk for migraine chronification. Methods Our aim is to conduct a comprehensive review of the available evidence regarding the underuse of migraine medications, both acute and preventive. The term “underuse” includes, but is not limited to: ( 1 ) ineffective use of appropriate and inappropriate medication; ( 2 ) underutilization; ( 3 ) inappropriate timing of usage; and ( 4 ) patient dissatisfaction with medication. Results The underuse of both acute and preventive medications has been shown to contribute to the progression of migraine. In terms of acute medication, chronification occurs as a result of insufficient drug use, including failure of the prescriber to select the appropriate type based on pain intensity and disability, patients taking medication too late (more than 60 minutes after the onset or after central sensitization has occurred as evidenced by allodynia), and discontinuation because of lack of effect or intolerable side effects. The underlying cause of inadequate effectiveness of acute medication lies in its inability to halt the propagation of peripheral activation to central sensitization in a timely manner. For oral and injectable preventive migraine medications, insufficient efficacy and intolerable side effects have led to poor adherence and discontinuation with subsequent progression of migraine. The underlying pathophysiology here is rooted in the repetitive stimulation of afferent sensory pain fibers, followed by ascending brainstem pain pathways plus dysfunction of the endogenous descending brainstem pain inhibitory pathway. Although anti-calcitonin gene-related peptide (CGRP) medications partially address pain caused by the above factors, including decreased efficacy and tolerability from conventional therapy, some patients do not respond well to this treatment. Research suggests that initiating preventive anti-CGRP treatment at an early stage (during low frequency episodic migraine attacks) is more beneficial than commencing it during high frequency episodic attacks or when chronic migraine has begun. Conclusions The term “medication underuse” is underrecognized, but it holds significant importance. Optimal usage of acute care and preventive migraine medications could potentially prevent migraine chronification and improve the treatment of migraine attacks.

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Central Sensitization in Migraine: A Narrative Review

Cited by 31 publications

References 78 publications

Association between central sensitization, pain sensitivity and balance control in patients with migraine

Association between central sensitization, pain sensitivity and balance control in patients with migraine

What do patients’ efficacy and tolerability ratings of acute migraine medication tell us? Cross-sectional data from the DMKG Headache Registry

Medication “underuse” headache

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