Association between Body Mass Index and Medication-Overuse Headache among Individuals with Migraine: A Cross-Sectional Study.

INTRODUCTION: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. METHODS: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd Edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. RESULTS: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.11; p = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤23.9 kg/m2), those with Q4 (BMI ≥28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04-3.17; p = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03-1.24), less than high school (OR, 1.08; 95%, 1.01-1.15), without depression (OR, 1.06; 95%, 1.01-1.12), and without anxiety (OR, 1.06; 95%, 1.01-1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. CONCLUSION: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

A study on the role of serum uric acid in differentiating acute inflammatory demyelinating polyneuropathy from acute-onset chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: Clinical symptoms and laboratory indices for acute inflammatory demyelinating polyneuropathy (AIDP), a variant of Guillain-Barré syndrome, and acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) were analyzed to identify factors that could contribute to early differential diagnosis. METHODS: A retrospective chart review was performed on 44 AIDP and 44 A-CIDP patients looking for any demographic characteristics, clinical manifestations or laboratory parameters that might differentiate AIDP from acutely presenting CIDP. RESULTS: In Guillain-Barré syndrome patients (N = 63), 69.84% (N = 44) were classified as having AIDP, 19.05% (N = 12) were found to have acute motor axonal neuropathy, 6.35% (N = 4) were found to have acute motor and sensory axonal neuropathy, and 4.76% (N = 3) were found to have Miller Fisher syndrome. Serum uric acid (UA) was higher in A-CIDP patients (329.55 ± 72.23 µmol/L) than in AIDP patients (221.08 ± 71.32 µmol/L) (p = 0.000). Receiver operating characteristic analyses indicated that the optimal UA cutoff was 283.50 µmol/L. Above this level, patients were more likely to present A-CIDP than AIDP (specificity 81.80%, sensitivity 81.80%). During the follow-up process, serum samples were effectively collected from 19 AIDP patients during the rehabilitation phase and 28 A-CIDP patients during the remission stage, and it was found that UA levels were significantly increased in A-CIDP (remission) (298.9 ± 90.39 µmol/L) compared with AIDP (rehabilitation) (220.1 ± 108.2 µmol/L, p = 0.009). CONCLUSION: These results suggest that serum UA level can help to differentiate AIDP from A-CIDP with high specificity and sensitivity, which is helpful for early diagnosis and guidance of treatment.

Status of diagnosis and preventative treatment for primary headache disorders: real-world data of unmet needs in China.

BACKGROUND: Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists. METHODS: In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021. RESULTS: The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of "Nervous headache" was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study. CONCLUSIONS: While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future.

The prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache: The survey of fibromyalgia comorbid with headache.

OBJECTIVE: The aims were to explore the prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache. BACKGROUND: Studies done in non-Chinese populations suggest that around one-third of patients with primary headache have fibromyalgia, but data from mainland China are limited. Investigations into the prevalence and clinical features of fibromyalgia in Chinese patients with primary headache would improve our understanding of these two complex disease areas and help guide future clinical practice. METHODS: This cross-sectional study included adults with primary headache treated at 23 Chinese hospitals from September 2020 to May 2021. Fibromyalgia was diagnosed using the modified 2010 American College of Rheumatology criteria. Mood and insomnia were evaluated employing the Hospital Anxiety and Depression Scale and the Insomnia Severity Index. RESULTS: A total of 2782 participants were analyzed. The fibromyalgia prevalence was 6.0% (166/2782; 95% confidence interval: 5.1%, 6.8%). Compared to primary headache patients without combined fibromyalgia, patients with primary headache combined with fibromyalgia were more likely to be older (47.8 vs. 41.7 years), women (83.7% [139/166] vs. 72.8% [1904/2616]), less educated (65.1% [108/166] vs. 45.2% [1183/2616]), and with longer-duration headache (10.0 vs. 8.0 years). Such patients were more likely to exhibit comorbid depression (34.3% [57/166] vs. 9.9% [260/2616]), anxiety (16.3% [27/166] vs. 2.7% [70/2612]), and insomnia (58.4% [97/166] vs. 17.1% [447/2616]). Fibromyalgia was more prevalent in those with chronic (rather than episodic) migraine (11.1% [46/414] vs. 4.4% [72/1653], p < 0.001) and chronic (rather than episodic) tension-type headache (11.5% [27/235] vs. 4.6% [19/409], p = 0.001). Most fibromyalgia pain was in the shoulders, neck, and upper back. CONCLUSIONS: The prevalence of fibromyalgia in mainland Chinese patients with primary headache was 6.0%. Fibromyalgia was more common in those with chronic rather than episodic headache. The most common sites of fibromyalgia pain were the neck, shoulders, and back.

Microglial P2Y14 receptor contributes to central sensitization following repeated inflammatory dural stimulation.

BACKGROUND: Recent studies have indicated that P2Y receptors in spinal microglia play a role in the development of neuropathic and inflammatory pain. However, it remains unclear whether P2Y receptors in microglia are involved in the pathogenesis of migraine. Therefore, the aim of this study was to investigate the role of microglial P2Y14 receptor in trigeminal cervical complex (TCC) in migraine. METHODS: We used a rat model of migraine induced by repeated inflammatory stimulation of the dura and examined the expression of P2Y14 receptor in the TCC in migraine rats by Western Blotting and immunofluorescence staining. Then, we determined the effect of P2Y14 antagonist PPTN on inflammatory soup (IS)-induced mechanical allodynia, microglial activation and ERK expression in TCC. RESULTS: The expression level of P2Y14 receptor increased significantly in microglia in TCC after 4 or 7 days of repeated IS stimulation of the dura. Application of PPTN significantly attenuated the decrease of periorbital pain threshold in migraine model rats. In addition, repeated IS stimulation of the dura induced the activation of microglia and the phosphorylation of the ERK1/2 in microglia in TCC, which were abolished by the application of PPTN. CONCLUSION: Our findings suggest that the increased P2Y14 receptor in microglia in TCC play a crucial role in the generation of mechanical allodynia in migraine rat model. Furthermore, the activation of the P2Y14 receptor is involved in microglial activation and ERK phosphorylation as well. The P2Y14 receptor in microglia might be used as a potential target for migraine treatment.

Corneal subbasal nerve plexus changes in patients with episodic migraine: an in vivo confocal microscopy study.

Background and purpose: It has been generally thought that activation and sensitization of the trigeminovascular system may contribute to the pathogenesis of migraine. Nevertheless, there is little evidence on abnormalities in peripheral trigeminal afferent nerves from humans in vivo. Alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve may support the notion that trigeminal afferent nerves are involved in migraine pathophysiology. The aim of the present study was to investigate the structural changes in corneal subbasal nerve plexus in patients with episodic migraine (EM) with in vivo confocal microscope (IVCM). Methods: In this cross-sectional observational study, 10 EM patients and 10 age- and sex-matched healthy controls were included. Analysis of IVCM images with Image J software was performed to quantify the changes in the corneal subbasal nerve plexus. Results: EM patients showed an increase in nerve fiber length (25.0±2.65 vs 22.3±2.41 mm/mm2, p=0.047) and nerve fiber density (36.3±7.29 vs 30.5±6.19 fibers/mm2, p=0.104) as compared with normal controls, but this difference was not statistically significant. Nerve branching and tortuosity were significantly increased in the EM subjects compared to the normal subjects (91.3±13.8 vs 75.0±14.2 branches/mm2, p=0.030 and 2.30±0.46 versus 1.63±0.52, p=0.011, respectively). In addition, nerve sprouts and increased number of Langerhans cells were observed in the EM patients. Conclusion: The morphologic changes of corneal subbasal nerve plexus and Langerhans cell aggregation suggest the presence of nerve regeneration and inflammation in EM. Furthermore, the alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve offer support for the hypothesis that the peripheral trigeminal system may be involved in the pathogenesis of migraine.

Analysis of microbiota in elderly patients with Acute Cerebral Infarction.

BACKGROUND AND AIMS: Recent evidence suggest that microbiota is associated with almost all major types of diseases, including cardiovascular diseases. However, its role in Acute Cerebral Infarction remains unexplored. It is important to understand the diversity and distribution of gut microbiota (GM) in patients with Acute Cerebral Infarction and the role that GM plays in this type of disease. METHODS: We performed pyrosequencing on the gut microbiota of 40 individuals in order to elucidate whether the composition of the microbiota differs between patients with Acute Cerebral Infarction and healthy controls: Of these individuals, there were 31 with Acute Cerebral Infarction and nine controls. We applied linear regression to calculate the correlation between the gut flora and disease risk factors. Finally, KEGG functional enrichment analysis was conducted to examine the correlation between the gut flora and Acute Cerebral Infarction. RESULTS: The overall microbial structure was similar in both the controls and the patients, but the control group had higher relative presence of Blautia obeum while the presence of Streptococcus infantis and Prevotella copri were relatively higher in the patient group. Using linear regression, we found that Blautia obeum was negatively associated with white blood cell count and Streptococcus infantis was positively correlated with creatinine and lipoprotein. The KEGG pathway analysis indicated that the bio-pathways including methane metabolism, lipopolysaccharide synthesis, bacterial secretion, and flagellar assembly of the gut microbiota in the patient group was expressed differently than that of the controls. We identified three differentially expressed gut microbial functions in Acute Cerebral Infarction and found four bacterial pathways that might be related to the development of this disease. CONCLUSIONS: Our study identified three abnormally-expressed bacteria-Blautia obeum, Streptococcus infantis, and Prevotella copri-in patients with Acute Cerebral Infarction compared with healthy controls. It reveals a correlation of these bacterial species with Acute Cerebral Infarction as they relate to disease factors and functional pathways. These findings may shed light on the treatment of cerebral infarction because gut microbiota could serve as a potential therapeutic approach for the treatment of cardiovascular and metabolic diseases.

Association between carotid plaque and Parkinson's disease.

BACKGROUND: Epidemiological studies show that patients with Parkinson's disease (PD) are prone to have a reduced incidence of ischemic cerebrovascular disease. Previous studies show the correlation between PD and the lipids serum levels. The PD,s patients are found with a reduced serum level of triglyceride and low-density lipoprotein cholesterol (LDL-C); thus, the level of serum uric acid (UA) is closely related to the occurrence and development of PD. Patients with low serum UA levels have a higher chance of developing PD than the ones who do not. However, the relationship between carotid plaques and PD is still unknown. METHODS: Our study was based on 68 patients with PD (known as the PD group) and 81 people without PD (known as the control group). Patients in the PD group were of the same age and gender. Both groups were recorded and analyzed for UA, LDL-C, and carotid plaques or intima-media thickness (IMT). The PD group was then divided into three subgroups: the stable plaque group, the unstable plaque group, and the non-plaque group. RESULTS: In the present study, the PD group showed a significantly lower level of UA and LDL-C than the control group (P<0.01); somehow there were no statistically significant differences in the IMT and plaque incidence between the two groups (P>0.05). There were also no significant differences (P>0.05) in both the LDL-C and UA levels in all subgroups, but there was a close relation in both age and duration of disease to IMT. According to the Hoehn and Yahr staging scale, serum levels of LDL-C were inversely correlated in PD patients, while UA was related to the duration of the disease. CONCLUSIONS: Our study suggested that there were no differences in carotid artery arteriosclerosis plaque and IMT, but the PD progress was indeed correlated with IMT. Meanwhile, LDL-C and UA had different priorities in H&Y and disease progression.

Repetitive transcranial magnetic stimulation for the treatment of Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Several studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) may have a beneficial effect in Alzheimer's disease (AD). Nevertheless, the clinical benefit of rTMS for AD remains inconclusive. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of rTMS in AD. METHODS: We searched PubMed, Embase and Cochrane for randomized controlled trials (RCTs) of rTMS for AD. We calculated pooled estimates of mean difference (MD) with 95% confidence intervals (CI). The protocol was registered at International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42018089990). RESULTS: Five RCTs involving 148 participants were included in this review. Compared with sham stimulation, high-frequency rTMS led to a significant improvement in cognition as measured by ADAS-cog (MD = -3.65, 95% CI -5.82 to -1.48, p = 0.001), but not MMSE (MD = 0.49, 95% CI -1.45 to 2.42, p = 0.62). High-frequency rTMS also improved the global impression in comparison to the placebo (MD = -0.79, 95% CI -1.24 to -0.34, p = 0.0006). There was no significant difference in mood (MD = -1.36, 95% CI -3.93 to 1.21, p = 0.30) and functional performance (MD = 0.59, 95% CI -1.21 to 2.38, p = 0.52) between high-frequency rTMS and sham groups. Only one trial included low-frequency rTMS reported no significant improvement in cognition, mood and functional performance. Few mild adverse events were observed in both the rTMS and sham groups. CONCLUSIONS: RTMS is relatively well tolerated, with some promise for cognitive improvement and global impression in patients with AD. Our findings also indicate the variability between ADAS-cog and MMSE in evaluating global cognitive impairment.

Paraneoplastic cerebellar degeneration associated with breast cancer: A case report and review of the literature.

Paraneoplastic cerebellar degeneration (PCD) is a rare neurological complication of cancer characterized by rapid development of cerebellar ataxia. We herein present a case of a 67-year-old female patient with PCD caused by breast cancer. The patient presented with progressively worsening cerebellar deficits that had been misdiagnosed for several months prior to the identification of the anti-Yo autoantibodies in the serum. A whole-body positron emission tomography/computed tomography scan revealed a lesion in the lower outer quadrant of the left breast with slightly increased metabolism. On mammography, a lobulated high-density mass was identified in the left breast. The patient underwent left breast lumpectomy and the histological examination confirmed the presence of an invasive ductal carcinoma. After breast surgery, the patient exhibited marked neurological improvement at the 12-month follow-up. Therefore, it is crucial that clinicians include paraneoplastic neurological syndromes in the differential diagnosis of neurological disorders. The detection of characterized onconeural antibodies in the serum or cerebrospinal fluid may provide guidance in the search for an underlying tumor.

Abnormal mitochondrial dynamics and impaired mitochondrial biogenesis in trigeminal ganglion neurons in a rat model of migraine.

Accumulating evidence has demonstrated a possible role of mitochondrial dysfunction in migraine pathophysiology. Migraine sufferers exhibit impaired metabolic capacity, with an increased formation of reactive oxygen species (ROS). Mitochondrial dynamics and mitochondrial biogenesis are key processes regulating mitochondrial homeostasis. The aim of this study was to explore the alterations of mitochondrial regulatory networks in a rat model of migraine induced by repeated dural stimulation with inflammatory soup (IS). Ultrastructural, protein, gene and mitochondrial DNA analysis were applied to assess mitochondrial dynamics and biogenesis in trigeminal ganglion (TG) neurons. Mitochondria in TG neurons exhibited small and fragmented morphology after repeated dural stimulation. Further investigations showed that mitochondrial fission protein dynamin-related protein 1 (Drp1) was increased while mitochondrial fusion protein Mitofusin1 (Mfn1) was reduced in TG neurons. In addition, our results also presented that mitochondrial DNA copy number in TG neurons was reduced significantly, accompanied by alterations in mRNA and protein levels of regulatory factors related to mitochondrial biogenesis including peroxisome proliferator-activated receptor-gamma coactivator-1a (PGC-1α) and its downstream regulators in TG neurons in the IS-induced migraine model. These findings suggest that the mitochondrial dynamic regulatory networks are maladjusted in TG neurons in a rat model of migraine. Regulation of mitochondrial dynamics and biogenesis signaling may indicate a new mitochondria-targeted therapeutic strategy for migraine.

Amitriptyline modulates calcium currents and intracellular calcium concentration in mouse trigeminal ganglion neurons.

Migraine is increasingly recognized as a channelopathy, and abnormalities of voltage-activated ionic channels could represent the molecular basis for the altered neuronal functioning. The high-voltage-activated (HVA) Ca(2+) channels in the trigeminovascular system play a role in the pathophysiology of migraine. In the present study, effects of amitriptyline (AMT), a commonly used migraine prophylactic drug, on the HVA calcium currents (I(Ca)) were examined in mouse trigeminal ganglion neurons using whole-cell patch clamp technique. AMT produced concentration- and use-dependent inhibition of HVA I(Ca). Bath application of GÖ-6983 (a selective protein kinase C inhibitor) or H89 (a protein kinase A inhibitor) did not reduce the AMT-induced inhibition of HVA I(Ca). A similar inhibition was observed when calcium imaging was used to directly monitor the effects of AMT on KCl-induced increments of intracellular Ca(2+) concentration ([Ca(2+)](i)). By blocking HVA Ca(2+) channels and Ca(2+) entry into cells, AMT could prevent the release of neurotransmitters and help restore the neuronal threshold for excitation. Our findings suggest interesting therapeutic mechanisms for AMT in migraine prevention.

Flunarizine inhibits sensory neuron excitability by blocking voltage-gated Na+ and Ca2+ currents in trigeminal ganglion neurons.

BACKGROUND: Although flunarizine has been widely used for migraine prophylaxis with clear success, the mechanisms of its actions in migraine prophylaxis are not completely understood. The aim of this study was to investigate the effects of flunarizine on tetrodotoxin-resistant Na(+) channels and high-voltage activated Ca(2+) channels of acutely isolated mouse trigeminal ganglion neurons. METHODS: Sodium currents and calcium currents in trigeminal ganglion neurons were monitored using whole-cell patch-clamp recordings. Paired Student's t test was used as appropriate to evaluate the statistical significance of differences between two group means. RESULTS: Both tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were blocked by flunarizine in a concentration-dependent manner with the concentration producing half-maximal current block values of 2.89 µmol/L and 2.73 µmol/L, respectively. The steady-state inactivation curves of tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were shifted towards more hyperpolarizing potentials after exposure to flunarizine. Furthermore, the actions of flunarizine in blocking tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were use-dependent, with effects enhanced at higher rates of channel activation. CONCLUSION: Blockades of these currents might help explain the peripheral mechanism underlying the preventive effect of flunarizine on migraine attacks.

Cervical sympathectomy reduces neurogenic vasodilation in dura mater of rats.

Migraine may affect the autonomic nervous system, but the mechanisms remain unclear. The sympathetic and parasympathetic nervous systems may play different roles in the attack. To explore the effect of blocking the cervical sympathetic nerve on vasodilation of the meningeal vessels, jugular vein calcitonin gene-related peptide (CGRP) and meningeal blood flow changes were measured before and after transection of the cervical sympathetic nerve by electrically stimulating the trigeminal ganglion in Sprague-Dawley (SD) rats. We found that CGRP level and meningeal blood flow increased in both the sham-operated and sympathectomized groups (p<0.05). Compared with the sham-operated group, dural blood flow decreased significantly in the cervical sympathectomy group, but CGRP level was not significantly different between these two groups. The cervical sympathetic nerve may play an important role in the process of neurogenic dural vasodilation in rats; this effect is not entirely dependent on CGRP level.

Flunarizine blocks voltage-gated Na(+) and Ca(2+) currents in cultured rat cortical neurons: A possible locus of action in the prevention of migraine.

Although flunarizine (FLN) has been widely used for migraine prophylaxis with clear success, the mechanisms of its actions in migraine prophylaxis are not completely understood. It has been hypothesized that migraine is a channelopathy, and abnormal activities of voltage-gated Na(+) and Ca(2+) channels might represent a potential mechanism of cortical hyperexcitability predisposing to migraine. The aim of the present study was to investigate the effects of FLN on Na(+) and Ca(2+) channels of cultured rat cortical neurons. Sodium currents (I(Na)) and calcium currents (I(Ca)) in cultured rat cortical neurons were monitored using whole-cell patch-clamp recordings. Both I(Na) and I(Ca) were blocked by FLN in a concentration-dependent manner with IC(50) values of 0.94µM and 1.77µM, respectively. The blockade of I(Na) was more powerful at more depolarizing holding potentials. The steady-state inactivation curve of I(Na) was shifted towards more hyperpolarizing potentials by FLN. FLN significantly delayed the recovery from fast inactivation of I(Na). Furthermore, the action of FLN in blocking I(Na) was enhanced at higher rates of channel activation. Blockades of these currents might help explain the mechanism underlying the preventive effect of FLN on migraine attacks.

Amitriptyline inhibits currents and decreases the mRNA expression of voltage-gated sodium channels in cultured rat cortical neurons.

Amitriptyline (AMI) is widely used for migraine prophylaxis, but its mechanism is undetermined. Cortical spreading depression (CSD), reflected by alterations in calcium, sodium, and Na(+)-K(+)ATP channels, has been implicated in migraine and as a headache trigger. Evidences indicate that mutations in sodium and calcium channels are involved in migraine. Sodium channels are critical for the electrical excitability of sensory neurons and play a key role in pain sensation by controlling afferent impulse discharge. To investigate the mechanism underlying AMI effectiveness for migraine prophylaxis, we studied the effects of AMI on voltage-gated sodium channels in cultured rat cortical neurons by the whole-cell patch clamp recording and real-time reverse transcription polymerase chain reaction (RT-PCR). We found that AMI blocked sodium channel current (I(Na)) in a concentration-dependent, not voltage-dependent manner. AMI also altered the activation and steady-state inactivation of I(Na) toward hyperpolarization. Results of real-time RT-PCR indicated that AMI inhibited the expression for sodium channels in a concentration-dependent manner; inhibition of expression of the Na(V)1.1 and Na(V)1.6 sodium channels was more than that of Na(V)1.2. From these results, we speculate that AMI may reduce CSD by inhibiting I(Na) and mRNA expression of sodium channels. This may contribute to strategies for migraine prophylaxis.