OBJECTIVES: To investigate the therapeutic mechanism of Huoxue Shufeng Granules (HXSFG) for alleviating central sensitization in a mouse model of chronic migraine (CM). METHODS: We analyzed the main chemical components of HXSFG through literature review and explored their pharmacological mechanisms by bioinformatics analyses. In a male C57BL/6J mouse model of CM established by intraperitoneal injections of nitroglycerin (10 mg/kg) every other day (5 injections), the effects of gavage with low, and high doses of HXSFG or intraperitoneal injections of topiramate for ameliorating central sensitization were evaluated using Von Frey test and a hot plate apparatus; the changes in expressions of inflammatory factors, the proteins in the TLR4/NF‑κB signaling pathway, and activation of c-Fos and CGRP were detected using RT-qPCR, Western blotting and immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that the main active components in HXSFG for alleviating CM included formononetin, paeoniflorin, quercetin, and tanshinone. Gene Ontology (GO) enrichment analysis identified 492 GO entries, comprising 366 biological processes, 46 cellular components, and 80 molecular functions. KEGG pathway enrichment analysis indicated that the Toll-like receptor and NF‑κB signaling pathways were crucial in mediating the therapeutic effects of HXSFG on CM. In the mouse models of CM, both topiramate and HXSFG treatments alleviated the symptoms of central sensitization, evidenced by improved mechanical and thermal pain thresholds in the mice. HXSFG significantly reduced the expression of c-Fos and CGRP, improved inflammatory markers, and downregulated the expressions of TLR4, p-NF‑κB, IL-1β, and TNF‑α proteins in the mouse models. CONCLUSIONS HXSFG effectively alleviates central sensitization in CM mice by modulating the inflammatory pathways and inhibiting the TLR4/ NF-κB signaling pathway, suggesting its potential as a therapeutic option for CM.
Animals ; Toll-Like Receptor 4/metabolism* ; NF-kappa B/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Male ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Migraine Disorders/metabolism* ; Disease Models, Animal ; Inflammation

Consensus ; Female ; Humans ; Male ; Migraine Disorders ; diagnosis ; epidemiology ; metabolism ; Vertigo ; diagnosis ; epidemiology ; metabolism ; Vestibular Diseases ; diagnosis ; epidemiology ; metabolism

Subclinical hypothyroidism (SCH) represents a mild or compensated form of primary hypothyroidism. The diagnosis of SCH is controversial, as its symptoms are non-specific and its biochemical diagnosis is arbitrary. The treatment of SCH was examined among non-pregnant adults, pregnant adults and children. In non-pregnant adults, treatment of SCH may prevent its progression to overt hypothyroidism, reduce the occurrence of coronary heart disease, and improve neuropsychiatric and musculoskeletal symptoms associated with hypothyroidism. These benefits are counteracted by cardiovascular, neuropsychiatric and musculoskeletal side effects. SCH is associated with adverse maternal and fetal outcomes that may improve with treatment. Treating SCH in children is safe and may improve growth. Importantly, the evidence in this field is largely from retrospective and prospective studies with design limitations, which precludes a conclusive recommendation for the treatment of SCH.
Adolescent ; Biomarkers ; metabolism ; Bone and Bones ; Child ; Coronary Disease ; blood ; Disease Progression ; Female ; Goiter ; complications ; Humans ; Hypothyroidism ; blood ; diagnosis ; therapy ; Male ; Migraine Disorders ; physiopathology ; Pregnancy ; Pregnancy Complications ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Treatment Outcome

In the paper, by taking acupuncture and migraine as the key words to retrieve CNKI and PubMed database, the literature analysis was done on the mechanism study on experimental migraine treated with acupuncture in rat model. The results showed that acupuncture mechanism study focused on the regulation and control of the relevant neurotransmitters/neuromodulators of migraine, such as calcitonin gene-related peptide (CGRP), serotonin (5-HT), nitric oxide (NO), etc. Moreover, in the paper, the review had been done on the neurotransmitters/neuromodulators involved in the study.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Disease Models, Animal ; Humans ; Migraine Disorders ; genetics ; metabolism ; therapy ; Nitroglycerin ; metabolism ; Rats ; Serotonin ; metabolism

OBJECTIVETo observe the effect of acupuncture along affected meridian on the mem- brane metallo-endopeptidase (MME) gene expression of migraine patients without aura (MO) of Gan-yang hyperactivity syndrome (GYHS).

METHODSTotally 20 MO patients of GYHS were randomly assigned to the acupoint group (acupuncture along affected meridian) and the non-acupoint group, 10 cases in each group. Needling was performed once per day for 10 consecutive days. Gene chip technology was used to obtain two sets of gene expression profiles and analyzed using Gene Ontology (GO).

RESULTSIn the acupoint group, MME gene expression decreased after needling (P = 0.0023).That gene was rich in the beta-amyloid metabolic process (P = 3.16E-05) and the peptide metabolic process (P = 0.009612). Its expression was not seen in the non-acupoint group.

CONCLUSIONThe effect of point selection along affected meridian could be achieved possibly by regulating the MME gene expression.

Acupuncture ; Acupuncture Points ; Acupuncture Therapy ; Endrin ; analogs & derivatives ; metabolism ; Humans ; Meridians ; Migraine Disorders ; therapy ; Syndrome

The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside (AS) based standardized extract of Centella asiatica (L.) Urban leaves (INDCA) in animal models of migraine. The effects of oral and intranasal (i.n.) pretreatment of INDCA (acute and 7-days subacute) were evaluated against nitroglycerine (NTG, 10 mg·kg(-1), i.p.) and bradykinin (BK, 10 μg, intra-arterial) induced hyperalgesia in rats. Tail flick latencies (from 0 to 240 min) post-NTG treatment and the number of vocalizations post-BK treatment were recorded as a measure of hyperalgesia. Separate groups of rats for negative (Normal) and positive (sumatriptan, 42 mg·kg(-1), s.c.) controls were included. The interaction of INDCA with selective 5-HT1A, 5-HT1B, and 5-HT1D receptor antagonists (NAN-190, Isamoltane hemifumarate, and BRL-15572 respectively) against NTG-induced hyperalgesia was also evaluated. Acute and sub-acute pre-treatment of INDCA [10 and 30 mg·kg(-1) (oral) and 100 μg/rat (i.n.) showed significant anti-nociception activity, and reversal of the NTG-induced hyperalgesia and brain 5-HT concentration decline. Oral pre-treatment with INDCA (30 mg·kg(-1), 7 d) showed significant reduction in the number of vocalization. The anti-nociceptive effects of INDCA were blocked by 5-HT1A and 5-HT1B but not 5-HT1D receptor antagonists. In conclusion, INDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.
Administration, Intranasal ; Administration, Oral ; Animals ; Bradykinin ; Female ; Hyperalgesia ; chemically induced ; prevention & control ; Male ; Migraine Disorders ; chemically induced ; prevention & control ; Models, Animal ; Nitroglycerin ; Nociception ; drug effects ; Plant Leaves ; chemistry ; Pre-Exposure Prophylaxis ; Rats ; Rats, Wistar ; Reaction Time ; Receptors, Serotonin, 5-HT1 ; drug effects ; Serotonin 5-HT1 Receptor Antagonists ; metabolism ; Tail ; physiology ; Triterpenes ; administration & dosage ; pharmacology

OBJECTIVETo observe the clinical effect and mechanism of migraine treated with pine needle moxibustion.

METHODSForty-three patients were randomly divided into 2 groups of pine needle moxibustion group (group A, 21 cases) and medicated thread moxibustion of Zhuang medicine group (group B, 22 cases). Same acu-points were selected as the main points for both groups, namely Fengchi (GB 20), Baihui (GV 20), Taiyang (EX-HN 5), Shuaigu (GB 8), Cuanzhu (BL 2), Sizhukong (TE 23), Yanglingquan (GB 34), Waiguan (TE 5) and Ashi points. Pine needle moxibustion was applied for the group A. Processed lighted pine needles were banded together with one even head to do moxibustion on acupoints or pain points. While, lighted medicated thread was adopted for the group B to do moxibustion. Therapeutic effects, the content of high-sensitivity C-reactive protein (hs-CRP), Mg2+ in the serum and the degree of pain of the two groups were compared.

RESULTS(1) In the group A, the complete remission rate was 47.6% (10/21) and the effective rate was 90.5% (19/21). In the group B, the complete remission rate was 13.6% (3/22) and the effective rate was 50.0% (11/22). The two rates in the group A were superior to those in the group B (both P < 0.01); (2) In the group A, the content of hs-CRP was decreased from (4.29 +/- 0.98) mg/L to (2.11 +/- 0.87) mg/L, and Mg2+ was increased from (0.67 +/- 0.28) mmol/L to (1.07 +/- 0.16) mmol/L. In the group B, the contents of the above mentioned indices were respectively decreased from (4.30 +/- 1.07) mg/L to (3.38 +/- 1.15) mg/L and increased from (0.68 +/- 0.21) mmol/L to (0.88 +/- 0.25) mmol/L. There were significant differences between the two groups after treatment (both P < 0.05). (3) The degree of pain in the group A after treatment was much lower than that in the group B (P < 0.05).

CONCLUSIONThe clinical effect of migraine treated with pine needle moxibustion is better than that with the medicated thread moxibustion of Zhuang medicine. And it has obvious regulation effect on the levels of hs-CRP and Mg2+ in the serum of patients.

Acupuncture Points ; Adolescent ; Adult ; C-Reactive Protein ; metabolism ; Female ; Humans ; Magnesium ; blood ; Male ; Middle Aged ; Migraine Disorders ; metabolism ; therapy ; Moxibustion ; Young Adult

We report on an angioedema patient with a genetic defect in complement 1 inhibitor, manifesting migraine-like episodes of headache, effective prophylaxis with Danazol, and triptan for a treatment of acute clinical episode. The patient was 44-yr-old Korean man with abdominal pain and headache, who was brought into the Emergency Department of Seoul National University Hospital, Seoul. He suffered from frequent attacks of migraine-like headache (3-7 per month), pulsating in nature associated with nausea. Severities were aggravated by activity and his headache had shown recent progression with abdominal pain. No remarkable findings were observed on radiologic examination, brain magnetic resonance images and intracranial and extracranial magnetic resonance angiography. Danazol 200 mg every other day was subsequently used. Following administration of Danazol, symptoms showed improvement and the patient was discharged. While taking Danazol, the migraine-like episodes appeared to be prevented for about 2 yr. At the eighth month, he suffered a moderate degree of migraine-like headache; however, administration of naratriptan 2.5 mg resolved his problem. A case of genetic defect of C1-INH deficiency presented with headache episodes, and was controlled by Danazol and triptan. It suggests that pathogenic mechanism of headache in hereditary angioedema may be mediated by the neurogenic inflammatory-like physiology of migraine.
Adult ; Angioedemas, Hereditary/*complications/diagnosis/*genetics ; Brain/radionuclide imaging ; Complement C1 Inhibitor Protein/*genetics/metabolism ; Danazol/therapeutic use ; Estrogen Antagonists/therapeutic use ; Humans ; Magnetic Resonance Angiography ; Male ; Migraine Disorders/*diagnosis/drug therapy/*etiology ; Piperidines/therapeutic use ; Tryptamines/therapeutic use ; Vasoconstrictor Agents/therapeutic use

OBJECTIVE: To detect the influence of heat coagulation of middle meningeal artery (MMA) on plasma CGRP and SP levels in migraine rat triggered by nitroglycerin (NTG). METHOD: Twenty-four female Wistar rats were randomly divided into four groups, with six rats in each group. In group A, rats were treated with isotonic saline; in group B, rats were injected subcutaneously with 10 mg/kg nitroglycerin to set up the animal model of migraine; in group C, rats were subjected to sham surgery by merely exposing MMA and then injected with nitroglycerin (10 mg/kg); and in group D, rats were firstly subjected to heat coagulation of MMA and, subsequently, injected with nitroglycerin (10 mg/kg). Following the injection, the animal's behavior was continuously recorded by an observer. Radioimmunoassay was employed to measure the amounts of CGRP and SP in venous plasma. RESULT: Injection of 10 mg/kg nitroglycerin was able to trigger the animal model of migraine as evidenced by the appearances of a series of symptoms, such as, scratching head frequently, climbing cage and red ear. Rats in group A occasionally showed off scratching head, whereas, rats from group B and group C presented with much severe symptoms. Of note, rats in group D appeared slightly scratching head and climbing cage, without red ear compared with group B and C. At the same time, the amounts of plasma CGRP and SP in group B, group C, or group D were increased significantly compared with that of group A (P < 0.05). Furthermore, the plasma CGRP and SP levels in group D were much lower than that in group B and group C (P < 0.05), but there was no statistical difference between group B and group C (P > 0.05). CONCLUSION Heat coagulation of MMA may relieve symptoms of rats following nitroglycerin infusion, possibly by inhibiting the release of CGRP and SP.
Animals ; Calcitonin Gene-Related Peptide ; blood ; metabolism ; Electrocoagulation ; Female ; Meningeal Arteries ; Migraine Disorders ; chemically induced ; metabolism ; therapy ; Nitroglycerin ; adverse effects ; Rats ; Rats, Wistar ; Substance P ; blood ; metabolism

BACKGROUNDCortical spreading depression can cause migraine attack, and up-regulate matrix metalloproteinase-9 (MMP-9) expression in animal. This study aimed to determine the impact on the structure and function of the blood-brain barrier by measuring plasma MMP-9 levels in patients at the acute and late stages of migraine attacks in order to elucidate the pathological mechanisms involved.

METHODSWe recruited a case-control cohort of 38 adult migraine patients and 20 age- and gender-matched healthy control subjects. Five milliliter blood samples were collected at the acute and late stages of migraine (days 1 - 7), and also from the control subjects. Solid phase double antibody sandwich enzyme-linked immunosorbent assay was used to determine plasma MMP-9 levels. Statistical analysis was performed using the SAS version 9.1.

RESULTSInitial plasma MMP-9 levels of migraine patients were significantly higher than those of controls ((12.612 ± 0.016) µg/L vs. (6.069 ± 0.023) µg/L, respectively, P < 0.05). High MMP-9 expression was observed during days 1 - 6 of migraine attacks, with highest expression occurring on day 3 ((17.524 ± 0.035) µg/L). During attacks, MMP-9 levels were similar in migraine patients with and without aura (P > 0.05); in addition, levels were not correlated with degree of headache pain (P > 0.05).

CONCLUSIONSWe hypothesize that migraine could lead to increased plasma MMP-9 levels resulting in blood-brain barrier damage. MMP-9 levels increase during days 1 - 6 of migraine attacks, peaking on day 3. Therefore, MMP-9 could be used as a biological marker to guide treatment of migraine attacks.

Adult ; Blood-Brain Barrier ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Migraine Disorders ; physiopathology ; Young Adult