The bio-active components of the Mongolian medicine Horcha-6 and therapeutic mechanism in the rat migraine model

Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treating migraines through the use of network pharmacology and a rat migraine model.Methods:After identifying the active components of Horcha-6,the corresponding genes of the active components’target were obtained from the Universal Protein database,and a“compound-target-disease”network was constructed using Cytoscape 3.9.0 software.For the in vivo experiments,nitroglycerin was injected intraperitoneally into rats to create a migraine model.Pre-treatment with Horcha-6 was administered orally for 14 days,and rats were subjected to migraine-related behavior tests.RNA sequencing was performed to identify the gene expression regulated by Horcha-6 in the trigeminal nerve.Results:A total of 903 chemical components of Horcha-6 have been collected in the liquid chromatography with tandem mass spectrometry.We discovered 55 of the Horcha-6 bio-active components that were evaluated based on their Percent Human Oral Absorption(≥30%)and DL values(≥0.185)on the traditional Chinese medicine systems pharmacology database.The“compound-target-disease”network contained 163 intersection targets with the migraine state.Gene Ontology analysis indicated that these components significantly regulated the immune response,vascular function,oxidative stress,etc.When Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed,we observed that most of the target genes were significantly enriched in the inflammation and neuro-related signaling pathway,toll-like receptor signaling pathway,neuroactive ligand-receptor interaction,etc.These predictions were further demonstrated via in vivo animal model experiments.The RNA sequencing results showed that 41 genes were down-regulated(P<0.05)and 86 genes were up-regulated(P<0.05)in the Horcha-6 treated group compared with the untreated group.Those genes were mainly involved in neuromodulation,vascular function,and hormone metabolism.Conclusion:The 55 bio-active components in Horcha-6 regulate inflammation,hormone metabolism,and neurotransmitters and have potential as a therapy to treat migraines.

Efficacy and safety of Yangxue Qingnao Granules in treatment of migraine:A systematic review and meta-analysis

BACKGROUND Yangxue Qingnao Granules(YXQN)is a Chinese patent medicine that has been commonly used in the clinical treatment of migraine.AIM To assess the efficacy and safety of YXQN alone for the treatment of migraine.METHODS We searched 10 databases to identify relevant randomized controlled trials(RCTs)published before September 2022.Two review authors independently searched and screened the literature,extracted the data,and assessed the methodological quality of the studies using criteria from ROB 2.0,and analyzed the data using Review Manager 5.4 software.RESULTS A total of 12 RCTs including 767 participants with migraine met the selection criteria.We divided these studies into comparisons of YXQN with placebo,routine treatment drugs,and other Chinese patent medicines.The meta-analysis showed the following:(1)Efficacy:The YXQN group outperformed the placebo group[relative risk(RR)=0.29,95%confidence interval(95%CI):0.15–0.43,P<0.00001],routine treatment group(RR=0.18,95%CI:0.09–0.27,P<0.0001),and Chinese patent medicine group(RR=0.27,95%CI:0.13–0.41,P<0.001);(2)frequency of headache:There was a significant difference between YXQN vs placebo[mean difference(MD)=-1.25,95%CI:-1.60 to-0.90,P<0.00001],routine treatment drugs(MD=-0.85,95%CI:-1.15 to-0.56,P<0.00001),and Chinese patent medicine(MD=-0.91,95%CI:-1.35 to-0.46,P<0.0001);(3)headache duration:We found great heterogeneity between studies,with no differences between YXQN and placebo(MD=-0.61,95%CI:-1.53 to-0.31,P=0.19)and routine treatment drugs(MD=-0.22,95%CI:-0.89 to 0.46,P<0.53).YXQN was more effective than other Chinese patent medicines in reducing headache duration(MD=-1.24,95%CI:-1.70 to-0.77,P<0.00001);and(4)headache severity:There was no significant difference between YXQN vs placebo(MD=-1.67,95%CI:-3.52 to 0.19,P=0.08),routine treatment drugs(MD=-0.53,95%CI:-2.02 to 0.96,P=0.68),and other Chinese patent medicines(MD=-0.49,95%CI:-2.83 to 1.85,P=0.68).Mild gastrointestinal adverse reactions were reported in three cases.CONCLUSION This study revealed that YXQN is effective and safe for treatment of migraine.

Clinical and Therapeutic Aspects of Migraine in Brazzaville

Introduction: Migraine is the most common primary headache, and can cause significant disability. There are two types, migraine without aura and migraine with aura. The diagnosis of migraine is essentially clinical. Worldwide prevalence was estimated at 11.6% in 2009. In Africa, it is estimated at 10.4%. Objective: To describe the clinical and therapeutic aspects of migraine in Brazzaville. Patients and Methods: This was a door-to-door cross-sectional study conducted from 1st May to 1 st July 2018 in the city of Brazzaville. Subjects over 18 with clearly expressed consent were included. The questionnaire covered demographic characteristics, diagnostic criteria for migraine according to the IHS, treatments taken. The degree of disability was determined using the Migraine Disability Assessment Scale (MIDAS). Statistical analysis was performed using SPSS 22.0 for MAC. Results: Of the 1017 subjects interviewed in this study, 115 (39.9%) had migraine, including 73 women (63.47%) and 42 men (36.52%). In the group of migraine sufferers, the number of cases of definite migraine was 61 (53.04%) and that of probable migraine 54 (46.95%). For 81 migraine sufferers (70.43%), stress was the triggering factor. The frequency of attacks was weekly and monthly for 30 (26.1%) and 19 (16.5%) sufferers respectively. The location of the migraine was unilateral in 38% of cases and tilted in 24.3%. The intensity of the attack was described as moderate and severe in 41.7% and 57.4% of subjects respectively. Phonophobia/photophobia accompanied the migraine in 65.2% of cases. One hundred and eight subjects were treated. Of these, 106 (98.1%) were on medication. Eleven (10.37%) had received a medical prescription, and ninety-seven (89.8%) were self-medicating. Five and three subjects were under the care of a general practitioner and a neurologist respectively. Conclusion: Migraine is a frequent pathology in Brazzaville. Its preponderance among young people and women calls for the implementation of effective prevention strategies for these already vulnerable social groups. The form without aura was the most common type. Visual aura was the most common type. Headache-related symptoms were dominated by phonophotophobia, followed by nausea and vomiting. Almost all migraine sufferers were self-medicating, and very few were under the care of a doctor. First-line analgesics and NSAIDs were the mainstay of treatment.

Exploring the mechanism of active ingredients of Smilacis Glabrae Rhizoma in treating migraine headache through network pharmacology and animal experiments

Background:To explore the potential mechanism of action of the active ingredients of Smilacis Glabrae Rhizoma(SGR)in the treatment of migraine using network pharmacology and in vivo experiments.Methods:Through the search of Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,Genecards,Drugbank and other databases,we obtained active ingredients,targets of SGR and related disease targets of migraine,and took the intersection for protein-protein interactions analysis.After constructing the network diagram,network topology analysis was performed to derive the core targets and key active ingredients,and Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed.Finally,molecular docking was performed and validated by in vivo experiments.In vivo experiments,18 male BALB/c mice were selected,and the SGR group was fed with SGR drinking tablet concentrate,and nitroglycerin injection was used to construct a mouse model of migraine.Enzyme-linked immunosorbent assay test was used to detect the levels of TNF-α,IL-1β,IL-6,and AKT1 in plasma.Results:The results showed that the core targets of SGR for the treatment of migraine were TNF-α,IL-1β,IL-6,and AKT1.These core targets and key active ingredients had better binding ability.Compared with the blank group,the number of head scratching in the model group increased.Compared with the model group,there was a significant reduction of the number of head scratching in the SGR group.In comparison with the blank group,the protein level in the plasma in the model group was markedly higher.Compared with the model group,the protein level in the SGR group was significantly lower.Conclusion:SGR has the characteristics of improving migraine based on multi-targets,multi-components and multi-pathways,and the mechanism of action may be related to the inhibition of the release of inflammatory factors,neuron protection,and interference with apoptosis and other processes.

Vestibular migraine in low-and lower-middle-income countries:A scoping review

Background:Vestibular migraine(VM)is a common cause of dizziness that is underrecognized,underdiagnosed,and challenging to effectively treat.The prevalence,appropriate diagnostic workup,and therapies for VM in low-and lower-middle-income countries(LLMICs)remain understudied.The objective of this scoping review is to evaluate the current state of VM research in LLMICs.Methods:PubMed,Embase,and Web of Science databases were searched to execute a scoping review of VM.Keywords“vestibular diseases”and“vertigo”were used in combination with terms referring to LLMICs as defined by the World Bank.Title and abstract screening,full-text review,and data collection were conducted by two authors independently.Results:Twenty-six studies were included in the scoping review.Most studies were cross-sectional(57.7%)or case studies/series(23.1%)and were conducted in urban settings only(92.3%).Geographic distribution of studies was skewed,with 65.4%of articles originating from India.The prevalence of VM among clinic patients ranged from 0.3%to 33.3%.VM most frequently presented as headache,nausea and vomiting,and photophobia.Radiographic imaging,audiometry,and electronystagmography/videonystagmography were the three most commonly utilized diagnostic modalities in the dizziness workup.The most studied pharmacotherapies included calcium channel blockers,followed by beta-blockers and antiepileptics.Case studies and series discussed less common VM pharmacotherapies,such as ayurvedic medicine.Conclusions:There is a need for more VM research in LLMICs,including innovative diagnostic approaches and therapies that can improve VM care globally.Equitable partnerships between LLMIC and highincome country researchers must expand vestibular research capacity and productivity in LLMICs.

Saccades of video head impulse test in Meniere's disease and Vestibular Migraine: What can we learn from?

Background:Saccades are often observed on video head impulse tests(vHIT)in patients with Meniere's Disease(MD)and Vestibular Migraine(VM).However,their saccadic features are not fully described.Objective:This study aims to identify the saccades characteristics of MD and VM.Methods:75 VM patients and 103 definite unilateral MD patients were enrolled in this study.First raw saccades were exported and analyzed.The VM patients were divided into left and right based on their ears,while the MD patients were separated into affected and unaffected subgroups based on their audiograms and symptoms.Results:The MD patients have more saccades on the affected side(85%vs.69%),and saccade velocity is more consistent than the contralateral side(shown by the coefficient of variation).The saccades occurrence rates on both sides are similar in VM(77%vs.76%),as are other saccadic parameters.The MD patients have more significant inter-aural differences than the VM patients,manifested in higher velocity(p-value 0.000),earlier arriving(p-value 0.010),and more time-domain gathered(p-value 0.003)on the affected side.Conclusions:Bilateral saccades are commonly observed in MD and VM.In contrast to MD,saccades on VM are subtle,scattered,and late-arrived.Furthermore,the MD patients showed inconsistent saccadic distribution with more velocity-uniform saccades on the affected side.

Integration of single-cell RNA sequencing and network disturbance to elucidate crosstalk between multi-components drug and trigeminal ganglia cells in migraine

OBJECTIVE To clarify the mecha⁃nism of Tou Tong Ning capsule(TTNC)and elu⁃cidate crosstalk between multi-components drug and trigeminal ganglia cells in migraine.METH⁃ODS We integrated single-cell RNA sequencing data and a quantitative evaluation algorithm of the disturbance of multi-target drugs on the dis⁃ease network to explore the specific pathology of TTNC for migraine.Cerebrovascular smooth muscle spasmolytic activity experiment was car⁃ried out to verify the results of bioinformatics analysis.RESULTS TTNC can effectively regu⁃late the functions of synaptic signaling,inflamma⁃tion and immune response,and cerebrovascular smooth muscle.For different cell subtypes of tri⁃geminal ganglia,TTNC can significantly disturb the robustness on neuronal cell networks and non-neural networks(fibroblast and vascular cells),indicating TTNC vasodilation activity of brain vessels and neural regulation activities of various neuro types.Contraction of cerebrovas⁃cular smooth muscle of mouse ex vivo confirmed the vasodilation activity of TTNC and active com⁃pounds(Emodin,Luteolin and Levistilide A).And literature mining confirmed the vasospasmolytic activity and neuroprotective effect activity of TTNC.CONCLUSIONS Integrating single-cell data and network disturbance tools provides a new strategy for the MoA of multi-components drug through cell subtyping.

Safety and Efficacy of Biodegradable Patent Foramen Ovale Occluder in Patients with Migraine:A Clinical Trial

Background:Transcatheter closure of patent foramen ovale(PFO)has been widely accepted as a highly effective way to treat high-risk PFO-related diseases.However,traditional non-degradable occluders made of metal alloys will permanently exist in the body,resulting in thrombosis,valve damage,hemolysis,arrhythmia,or other complications.The biodegradable PFO occluder developed by Shanghai Mallow Medical Instrument Co.,Ltd.,China can be fully absorbed and degrade into nontoxic ingredients,reducing postoperative complications.Objectives:To study the safety and efficacy of biodegradable PFO occluders in treating PFO.Methods:This single-center clinical trial collected 30 patients treated with a biodegradable PFO occluder.The follow-up period lasted 12 months to analyze the echocardiographic characteristics and headache relief through HIT-6 scores.Results:The immediate success rate was 100%,with no intraoperative severe occlusion-related complications.The contrast transcranial Doppler(cTCD)at 12 months showed that all patients’right-to-left shunts(RLS)were grade I or 0 with no serious postoperative complications,indicating the overall success rate was 100%.The biodegradable PFO occluder mostly degraded six months after the occlusion.Conclusion:PFO closure with a Mallow biodegradable occluder is safe and effective and has no severe complications.

Retinal and Choroidal Alterations in Migraine Patients Compared to Normal Healthy Controls

Purpose: Migraine is an incapacitating neurovascular disorder that primarily affects the working-age population. Researchers have postulated that the transient vascular alterations during each migraine attack lead to ischemic damage in the eye which can be measured via optical coherence tomography. Methods: We recruited 29 volunteers: 13 migraineurs (mean age 28 ± 8.8 years;12 female and 1 male) and 16 age-matched controls (mean age 26.6 ± 6.9;9 female and 7 male). All individuals underwent a detailed ophthalmic examination by a qualified optometrist and a Migraine Disability Assessment. The investigators were blind to the migraine diagnosis. Retinal Nerve Fiber Layer (RNFL) thickness, Retinal Thickness (RT), Ganglion Cell Complex (GCL), ranging from the inner-limiting membrane to the inner plexiform layer, and Choroidal Thickness (CT) were measured using the 3D OCT-1Maestro, Topcon, a Spectral Domain OCT (SD-OCT) device. Results: In the migraine population average RNFL was lower for several parameters. However, results did not reach statistical significance. A significant decrease in the right eye inferior parafoveal ganglion cell layer in the migraine group of patients (mean = 25.15, SD = 4.08) compared to normal healthy controls (mean = 28.81, SD = 4.85;t = (27) = 2.17, p = 0.039) was documented. No other ganglion cell layer or choroidal thickness reached significance. No significant relationship between ocular thickness parameters and MIDAS score, parameters and either MIDAS score or frequency of headaches was found. Conclusion: A significant decrease in the right inferior parafoveal ganglion cell layer for migraine patients was reported. All other parameters did not reach significance. .

Systematic Review and Meta-analysis on the Efficacy and Safety of Xuefu Zhuyu Oral Liquid(血府逐瘀口服液)in the Treatment of Migraine

Objective:To systematically evaluate the efficacy and safety of Xuefu Zhuyu Oral Liquid(血府逐瘀口服液)in the treatment of migraine.Methods:All randomized controlled trials(RCTs)on the treatment of migraine with Xuefu Zhuyu Oral Liquid were screened out by systematically searching Cochrane Library,Pub Med,Embase,Web of Science,VIP,Wanfang,CNKI and CBM database from database establishment to March 2023.Literature screening was conducted strictly according to inclusion and exclusion criteria,and the quality of the finally included RCTs was evaluated according to the Cochrane Handbook.All data analyses were completed using Rev Man 5.4 software provided by the Cochrane Collaboration.Results:A total of 8 RCTs involving 706 patients were included.Meta-analysis showed that Xuefu Zhuyu Oral Liquid alone(RR=1.22,95%CI[1.11,1.33],P<0.0001)or combined with conventional treatment(RR=1.19,95%CI[1.11,1.28],P<0.0001)was superior to conventional treatment alone in improving the severity of headache attacks and reducing recurrence.Three studies mentioned mild adverse reactions in individual patients during the treatment process,such as transient diarrhea,lethargy,etc.,which were not directly related to Xuefu Zhuyu Oral Liquid.Conclusion:Based on the existing data and meta-analysis results,Xuefu Zhuyu Oral Liquid alone or combined with conventional treatment can improve the total effective rate of migraine treatment,alleviate headache symptoms,reduce recurrence and adverse events.In the future,large-scale and high-quality original studies are needed to further verify the efficacy and safety of Xuefu Zhuyu Oral Liquid in the treatment of migraine,and provide a reference for the clinical medication of migraine.

Non-Traditional Management of Vestibular Migraine (Review)

Objectives: Vestibular migraine is one of the most common causes of episodic vertigo in adults and even in children. Traditional;management may have a side effect on the long run. So the aim of this review is to explain the other non-medical lines of management for patients with migraine. Methods: English articles from Medline and Cochrane library were searched and reviewed. Results: Evidence indicates that non-traditional management has a prophylactic and therapeutic effect on migraine patients with all its steps. Conclusion: Due to the possible side effects of pharmacological drugs and drug addictions, the use of non-traditional management alone or in combination with normal cures have been proposed. However, further constructive studies are required.

Clinical Research on Treatment of Migraine with Combination of Characteristic and Superior Techniques of Zhuang Medicine

Objective:To study the application effect of the combination of special advantages of Zhuang medical technology for migraine patients.Methods:80 patients with migraine were selected and all were admitted to Mingxiu Branch of International Zhuang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from February 2019 to February 2020.Random number table method was used to divide patients into two groups,with 40 patients in each group.Among them,the patients in the study group were treated with the therapy combining characteristics of Zhuang medicine and superior technology,that is,Zhuang medicine meridian tendon therapy+Zhuang medicine lotus needle cupping blood stasis removal therapy+Zhuang medicine thread moxibustion therapy+Zhuang medicine acupuncture therapy;the patients in the control group were treated with conventional Western medicine.The efficacy of the two treatments were compared.Results:After treatment,the total effective rate of clinical treatment in the study group was higher than that in the control group(P<0.05),and the visual analogue scale(VAS)score and integral improvement rate were higher than those in the control group(P<0.05).The onset time of action was statistically shorter than that of the control group(P<0.05).There was a statistically significant difference in the adverse reaction rate between the two groups(P<0.05).Conclusion:The combination of Zhuang medicine’s characteristic and superior techniques for patients with migraine has a significant curative effect.

Contributions of aversive environmental stress to migraine chronification:Research update of migraine pathophysiology

Clinical studies have suggested that internal and/or external aversive cues may produce a negative affective-motivational component whereby maladaptive responses(plasticity)of dural afferent neurons are initiated contributing to migraine chronification.However,pathophysiological processes and neural circuitry involved in aversion(unpleasantness)-producing migraine chronification are still evolving.An interdisciplinary team conducted this narrative review aimed at reviewing neuronal plasticity for developing migraine chronicity and its relevant neurocircuits and providing the most cutting-edge information on neuronal mechanisms involved in the processing of affective aspects of pain and the role of unpleasantness evoked by internal and/or external cues in facilitating the chronification process of migraine headache.Thus,information presented in this review promotes the understanding of the pathophysiology of chronic migraine and contribution of unpleasantness(aversion)to migraine chronification.We hope that it will bring clinicians’attention to how the maladaptive neuroplasticity of the emotion brain in the aversive environment produces a significant impact on the chronification of migraine headache,which will in turn lead to new therapeutic strategies for this type of pain.

Greater occipital nerve blocks in the treatment of refractory chronic migraine: An observational report of nine cases

AIM To report the effects of greater occipital nerve(GON) blocks on refractory chronic migraine headache.METHODS Nine patients who were receiving the conventionally accepted preventive therapies underwent treatment with repeated GON block to control chronic migraine resistant to other treatments. GON blocking with lidocaine and normal saline mixture was administered by the same physician at hospital once a month(for three times in total). Patients were assessed before the injection and every month thereafter for pain frequency and severity, number of times analgesics were used and any appearant side effects during a 6 mo follow-up.RESULTS Eight of nine patients reported a marked decrease in frequency and severity of migraine attacks in comparison to their baseline symptoms; one reported no significant change(not more than 50%) from baseline and did not accept the second injection. GON block resulted in considerable reduction in pain frequency and severity and need to use analgesics up to three months after the injection in the present cases. The patients did not report any adverse effects. CONCLUSION Hereby we noticed a remarkable success with refractory chronic migraine patients. We believe that this intervention can result in rapid relief of pain with the effects lasting for perhaps several weeks or even months. Further controlled clinical trials are warranted to evaluate the effect of GON block in the treatment of refractory migraine cases.

Regional volume changes of the brain in migraine chronification

The pathophysiology of migraine is complex.Neuroimaging studies reveal functional and structural changes in the brains of migraine patients.We sought to explore regional volume differences in intracranial structures in patients with episodic and chronic migraine.Sixteen episodic migraine patients,16 chronic migraine patients,and 24 normal controls were recruited and underwent 3.0 T MRI scanning.The volumes of 142 brain regions were calculated by an automatic volumetric algorithm and compared with clinical variables.Results demonstrated that the volumes of specific regions in the frontal and occipital lobes,and the right putamen,were increased and the volume of the fourth ventricle was decreased in the episodic migraine patients compared with controls.The volumes of the left basal forebrain,optic chiasm,and,the fourth ventricle were decreased in the chronic migraine patients,while the occipital cortex and the right putamen were larger.Compared to episodic migraine patiants,chronic migraine patients displayed larger left thalamus and smaller frontal regions.Correlation analysis showed that headache frequency was negatively correlated with the volume of the right frontal pole,right lateral orbital gyrus,and medial frontal lobes and positively correlated with the volume of the left thalamus.The sleep disturbance score was negatively correlated with the volume of the left basal forebrain.This suggests that migraine patients have structural changes in regions associated with pain processing and modulation,affective and cognitive processing,and visual perception.The remodeling of selective intracranial structures may be involved in migraine attacks.This study was approved by the Ethics Committee of Chinese PLA General Hospital(approval No.S2018-027-02)on May 31,2018.

Analysis of video head impulse test saccades data in patients with vestibular migraine or probable vestibular migraine

Objective:Saccades accompanied by normal gain in video head impulse tests(vHIT)are often observed in patients with vestibular migraine(VM).However,they are not considered as an independent indicator,reducing their utility in diagnosing VM.To better understand clinical features of VM,it is necessary to understand raw saccades data.Methods:Fourteen patients with confirmed VM,45 patients with probable VM(p-VM)and 14 agematched healthy volunteers were included in this study.Clinical findings related to spontaneous nystagmus(SN),positional nystagmus(PN),head-shaking nystagmus(HSN),caloric test and vHIT were recorded.Raw saccades data were exported and numbered by their sequences,and their features analyzed.Results:VM patients showed no SN,PN or HSN,and less than half of them showed unilateral weakness(UW)on caloric test.The first saccades from lateral semicircular canal stimulation were the most predominant for both left and right sides.Neither velocity nor time parameters were significantly different when compared between the two sides.Most VM patients(86%)exhibited small saccades,around 35%of the head peak velocity,with a latency of 200e400 ms.Characteristics of saccades were similar in patients with p-VM.Only four normal subjects showed saccades,all unilateral and seemingly random.Conclusions:Small saccades involving bilateral semicircular canals with a scattered distribution pattern are common in patients with VM and p-VM.

Electroacupuncture at Fengchi(GB20) inhibits calcitonin gene-related peptide expression in the trigeminovascular system of a rat model of migraine

Most migraine patients suffer from cutaneous allodynia; however, the underlying mechanisms are unclear. Calcitonin gene-related peptide（CGRP） plays an important role in the pathophysiology of migraine, and it is therefore, a potential therapeutic target for treating the pain. In the present study, a rat model of conscious migraine, induced by repeated electrical stimulation of the superior sagittal sinus, was established and treated with electroacupuncture at Fengchi（GB20）（depth of 2–3 mm, frequency of 2/15 Hz, intensity of 0.5–1.0 m A, 15 minutes/day, for 7 consecutive days）. Electroacupuncture at GB20 significantly alleviated the decrease in hind paw and facial withdrawal thresholds and significantly lessened the increase in the levels of CGRP in the trigeminal ganglion, trigeminal nucleus caudalis and ventroposterior medial thalamic nucleus in rats with migraine. No CGRP-positive cells were detected in the trigeminal nucleus caudalis or ventroposterior medial thalamic nucleus by immunofluorescence. Our findings suggest that electroacupuncture treatment ameliorates migraine pain and associated cutaneous allodynia by modulating the trigeminovascular system ascending pathway, at least in part by inhibiting CGRP expression in the trigeminal ganglion.

Midbrain enkephalin expression in a rat migraine model following intragastric scorpion powder administration

Scorpion has strong analgesic effects, but its analgesic mechanisms remain unclear. This study investigated the effects of scorpion powder on enkephalin expression in the midbrain of rats with nitroglycerin-induced migraine at mRNA and protein levels. Results confirmed that migraine rat abnormal behavior was significantly improved, and proenkephalin mRNA expression was significantly increased following treatment with scorpion. The number of methionine-enkephalin- positive cells in the migraine rats following treatment with scorpion was significantly increased, but no significant difference in the number of leucine-enkephalin-positive cells was detectable compared with migraine and normal rats. Taken together, these results show that scorpion exerts potentially beneficial effects by promoting enkephalin expression in nitroglycerin-induced migraine rats.

Gabapentin inhibits central sensitization during migraine

Peripheral and central sensitizations are phenomena that occur during migraine. The role of gabapentin, a migraine preventive drug, on central sensitization remains unclear. In this study, a rat model of migraine was established by electrical stimulation of the trigeminal ganglion, and the animals were given intragastric gabapentin. Changes in amino acid content in the cerebrospinal fluid and protein kinase C membrane translocation in the spinal trigeminal nucleus were examined to clarify the mechanisms underlying the efficacy of gabapentin in the treatment of central sensiti- zation during migraine. Electrophysiology, liquid chromatography-mass spectrometry and western blot analysis results revealed that gabapentin reduces neuronal excitability in the spinal nucleus in the trigeminal nerve, decreases excitatory amino acid content and inhibits the activation of protein kinase C. This provides evidence that excitatory amino acids and protein kinase C are involved in the formation and maintenance of central sensitization during migraine. Gabapentin inhibits mi- graine by reducing excitatory amino acid content in the cerebrospinal fluid and inhibiting protein kinase C activation.

Rizatriptan benzoate influences the endogenous pain modulatory system in a rat model of migraine

The present study utilized a nitroglycerin-induced rat model of migraine to detect the effects of rizatriptan benzoate on proenkephalin and substance P gene expression in the midbrain using real-time quantitative polymerase chain reaction and investigate whether rizatriptan benzoate can regulate the endogenous pain modulatory system. The results showed that rizatriptan benzoate significantly reduced expression of the mRNAs for proenkephalin and substance P. Rizatriptan benzoate may inhibit the analgesic effect of the endogenous pain modulatory system.