OBJECTIVES: To investigate the role of a neural pathway from oxytocin (OXT) neurons in the paraventricular hypothalamic nucleus (PVN) to γ-aminobutyric acid (GABA) neurons (GABAergic neurons) in the trigeminal nucleus caudalis (TNC) in regulating pain sensitization in a mouse model of chronic migraine and to explore the underlying mechanisms. METHODS: A chronic migraine mouse model was established by intraperitoneal injection of nitroglycerin (NTG, 1 mg/mL, 10 mg/kg) on days 1, 3, 5, 7, and 9. The study consisted of four parts: PartⅠ: 24 male wild-type C57BL/6J mice were divided into four groups (n=6 in each), receiving single or repeated injection of NTG or saline, respectively. Immunofluorescence was used to detect c-Fos and OXT expression in the PVN. Part Ⅱ: 6 male OXT-Cre transgenic C57BL/6J mice were used for anterograde monosynaptic tracing combined with RNAscope and immunofluorescence to identify neural projections from PVN OXT neurons to TNC GABAergic neurons. Part Ⅲ: 30 male OXT-Cre transgenic C57BL/6J mice were bilaterally injected Cre-dependent chemogenetic activation virus into the PVN. These mice were randomly divided into five groups, with six mice in each group. Mice in the clozapine N-oxide (CNO) group and the control group were intra-peritoneally injected with 0.1 mg/mL of CNO solution (1 mg/kg) and the same volume of isotonic normal saline, respectively. 3 hours after the injection, the brain tissues were harvest and c-Fos immunofluorescence staining was performed to verify the efficiency of chemogenetic activation virus. Mice in the model control group and the CNO activated model group were subjected to chronic migraine modeling, with bilateral TNC injection of isotonic normal saline and CNO, respectively, on day 10. The mice in the negative control group were bilaterally intra-TNC injected with isotonic normal saline. After 30 minutes, the Von-Frey filament and acetone tests were used to assess the mechanical pain threshold and cold pain response time in the periorbital region of the mice in these three groups. Part Ⅳ: 24 male OXT-Cre transgenic C57BL/6J mice were bilaterally injected with the Cre-dependent chemogenetic activation virus into the PVN. These mice were randomly divided into four groups, with six mice in each group. Mice in the model control group, the CNO activated model group and the atosiban group were subjected to chronic migraine modeling. On day 10, mice in the negative control group and the model control group were intraperitoneally injected with isotonic normal saline, while mice in the CNO activated model group and the atosiban group were intraperitoneally injected with CNO. After 15 minutes, mice in the atosiban group were bilaterally intra-TNC injected with atosiban, while mice in other three groups were bilaterally intra-TNC injected with isotonic normal saline containing 1% dimethyl sulfoxide. After 15 minutes, the Von-Frey filament and acetone tests were used to assess the mechanical pain threshold and cold pain response time in the periorbital region of the mice. The GABA content in the bilateral TNC was detected by high-performance liquid chromatography (HPLC). RESULTS: Mice with chronic migraine models exhibited reduced periorbital mechanical pain thresholds and increased periorbital cold pain reaction time, accompanied by an increase in both the number of c-Fos⁺ neurons and the percentage of c-Fos⁺ OXT neurons in the PVN (all P<0.05). The anterograde tracing virus and RNAscope combined with immunofluorescence staining showed that PVN OXT neurons projected to TNC GABAergic neurons. Immuno-fluorescence staining demonstrated that compared with the control group, the percentage of c-Fos⁺ OXT neurons in the PVN of CNO group increased (P<0.05). In bilateral intra-TNC drug administration experiments, compared with the model control group, the periorbital mechanical pain threshold increased, and the periorbital cold pain reaction time decreased in the CNO activated model group (both P<0.05). In intraperitoneal drug administration experiments, compared with the CNO activate model group, the periorbital mechanical pain threshold decreased, and the periorbital cold pain reaction time increased in the atosiban group (both P<0.05). HPLC analysis showed that, compared with the negative control group, the model control group and the atosiban group, GABA level of TNC in the CNO activated model group increased (all P<0.05). CONCLUSIONS PVN OXT neurons exert a descending facilitatory effect on GABAergic neurons in the TNC via OXT release, thereby ameliorating pain sensitization in chronic migraine.
Animals ; Paraventricular Hypothalamic Nucleus/physiopathology* ; Male ; Mice, Inbred C57BL ; Migraine Disorders/physiopathology* ; Mice ; GABAergic Neurons/physiology* ; Oxytocin/physiology* ; Disease Models, Animal ; Neurons/physiology* ; Mice, Transgenic ; Neural Pathways ; Chronic Disease

Objective:To investigate the potential characteristic manifestations and application value of the Dynamic Visual Acuity Test（DVAT） in vestibular migraine（VM）. Methods:A total of 50 VM patients（case group） and 50 healthy subjects（control group） diagnosed at the Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University between November 1, 2023, and December 31, 2024, were enrolled. The case group underwent DVAT, video head impulse test（vHIT）, caloric test, and Dizziness Handicap Inventory（DHI） assessment, whereas the control group only received DVAT. Group-based analyses were conducted to examine the effect of age on Dynamic Visual Acuity Loss（DVALoss）, as well as the correlations of DVALoss with vestibular function tests and DHI scores. Results:DVALoss in the case group was significantly higher than that in the control group（P<0.001）. In both groups, age was significantly and positively correlated with DVALoss（P<0.001）. Within the case group, DVALoss was strongly and positively correlated with DHI scores（r=0.807, P<0.001）; it was negatively correlated with the vestibulo-ocular reflex（VOR） gain in vHIT, though without clinical significance, and showed no significant association with the caloric test. Age and DVALoss collectively accounted for 71.3% of the variance in DHI scores（R²=0.713）, with age exerting a relatively minor actual impact. Conclusion:DVAT can sensitively identify the core functional impairments of VM. DVALoss, as a direct functional reflection of the pathological mechanism of VM, is strongly correlated with DHI scores. Incorporating DVALoss into standardized assessments may provide an objective basis for the diagnosis and management of VM.
Humans ; Migraine Disorders/diagnosis* ; Visual Acuity ; Case-Control Studies ; Head Impulse Test ; Vestibular Function Tests ; Female ; Male ; Adult ; Vestibular Diseases/physiopathology* ; Middle Aged ; Caloric Tests

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

OBJECTIVE: To analyze the characteristics of vestibular migraine (VM), in order to understand the auditory and vestibular function. METHOD: One hundred cases of confirmed or suspected VM patients were observed. Routine examination including pure tone test, vestibular dual temperature test and vestibular evoked myogenic potential(VEMP) and video head impulse test(v-HIT) Were conducted. RESULT: The incidence of male and female was about 1.00 : 2. 57. The average age of onset was 47 years, of which the youngest was 19 years old, and the oldest was 74 years old. Ninty-three cases of patients presented with vestibular sensitive performance, including photophobia, phonophobia,or motion sensitive. Fourty-two patients had migraine at the onset of the disease. Thirty-four patients had cochiear symptoms, including tinnitus, ear fullness, or epicophosis. In seventeen cases of fatigue, tension or poor sleep can cause vertigo. Nine patients had low blood pressure, 7 patients presented with hypertension. Two cases of vertigo were closely related to the change of position, and 1 case had visual aura. In the experiment, 94 patients had undergone VEMP test,with 44 cases of abnormal VEMP value. Seventy-nine patients had been examined v-HIT,of whom 2 patients were abnormal (both of which were reduced). Pure tone audiometry was abnormal in 35 cases. Five cases of patients showed abnormal vestibular-double temperature test. CONCLUSION Vestibular migraine is more prone to female, with young middle age, and can be accompanied by cochlear symptoms. Vestibular function tests (low frequency and high frequency) are normal.
Adult ; Aged ; Audiometry, Pure-Tone ; Evoked Potentials ; Female ; Head Impulse Test ; Humans ; Male ; Middle Aged ; Migraine Disorders ; diagnosis ; Vestibular Function Tests ; Vestibule, Labyrinth ; physiopathology ; Young Adult

OBJECTIVE: To compare the features of caloric tests in vestibular migraine (VM) and Menière's disease (MD) patients, and provide objective evidence for differentiating the 2 groups of patients. METHOD: This case-control study included 11 MD patients with left ear involved and mild to moderate impaired hearing, and 18 matched cases with VM. All participants received caloric tests. Maximum slow phase velocities (SPVmax) were used to describe horizontal and vertical nystagmus respectively and were compared between the 2 groups. Horizontal and vertical canal parasis(CP) were calculated according to respective SPVmax. Unilateral (UW-VR) or bilateral (BW-VR) weakness of vestibular response, and positive unilateral (UVR) or bilateral (BVR) vertical response or negative bilateral vertical response (NBVR) were judged by the boundary point of SPVmax of 5°/s respectively. Total left (LV) or right (RV) Vertical reactions were calculated accoeding to vertical SPVmax,and inter ears difference of vertical responses (IED-VR) calculated from LV minus RV. RESULT: There were no significant differences in age and gender between the 2 groups. Horizontal SPVmax of all of caloric tests of VM group,except the left cold (LC), were statistically larger than that of MD group (P < 0.05) and the maximum responses of right warm (RW) caloric test in VM group (34.50 ± 17.77) were significantly greater than that in MD group (12.82 ± 6.69) (P < 0.01). Only the vertical SPVmax of RW of all caloric tests has statistically difference between the 2 groups (P < 0.01), and the maximum responses of RW caloric test in VM group (6.00 ± 4.45) were significantly stronger than that of LC in MD group (1.27 ± 2.00) (P < 0.01). Horizontal CP ≥ 25% of the 2 groups(VM: 72.22%, MD: 54.55%) were not statistically different, while the proportions of UW-VR and BW-VR in VM group (5.56%, 0) were significantly lower than that in MD group (27.27%, 18.18%) (P < 0.05). Vertical CP ≥ 25% of the 2 groups (VM: 94.44%, MD: 27.27%) were significantly different (P < 0.01), and the proportions of positive UVR (left: 5.56%, right: 77.78%) and BVR (0) and NBVR (16.67%) in VM group were significantly different from that in MD group (UVR (left: 9.09%, right: 0), BVR (0), NBVR (90.91%)) (P < 0.01). There was statistically difference between LV and RV in VM group (P < 0.01, LV < RV), while no difference were showed in MD group. IED-VR in VM group (left intenser: 16.67%, right intenser: 83.33%) was statistically different from that in MD group (left intenser: 36.36%, right intenser: 9.09%, both no difference: 54.55%) (P < 0.01). CONCLUSION Vestibular responses of caloric test are more sensitive, and vertical reactions are more easily induced in VM patients than in MD. Caloric test can be used to differentiate the 2 groups of diseases.
Caloric Tests ; Case-Control Studies ; Diagnosis, Differential ; Humans ; Meniere Disease ; diagnosis ; physiopathology ; Migraine Disorders ; diagnosis ; physiopathology

Adult ; Carotid Artery, Internal ; pathology ; physiopathology ; Headache ; pathology ; physiopathology ; Humans ; Male ; Migraine Disorders ; pathology ; physiopathology

OBJECTIVETo observe the differences in clinical effect on menstrual migraine between subgaleal acupoint injection with metoclopramide and oral administration of medication.

METHODSSixty-four patients of menstrual migraine were randomized into a subgaleal acupoint injection group and a medication group, 32 cases in each one. In the subgaleal acupoint injection group, the acupoint injection started 10 days before menstruation. Eight acupoints on the head were selected and injected alternatively in two groups, once every 2 days, 4 treatments made one session and 3 sessions (3 menstrual cycles) were required. In the medication group, flunarizine was applied with oral administration, 2.5 mg each time, once every night. The duration of treatment was 3 months. The analgesic effect, frequency and time of pain attack were observed in 3 and 6 months after treatment in the two groups.

RESULTSAfter treatment, VAS scores were lower than those before treatment in the two groups (P<0.01, P<0.05), the attack frequency and pain time were all reduced as compared with those before treatment (all P<0.01). After treatment, VAS score, the frequency and time of pain attack in the subgaleal acupoint injection group were improved significantly as compared with the medication group (all P<0.01).

CONCLUSIONThe subgaleal acupoint injection with metoclopramide achieves the superior preventive effect in clinical treatment of menstrual migraine as compared with flunarizine.

Acupuncture Points ; Adolescent ; Adult ; Female ; Humans ; Menstruation ; drug effects ; Metoclopramide ; administration & dosage ; Migraine Disorders ; drug therapy ; physiopathology ; prevention & control ; Young Adult

OBJECTIVETo establish the migraine rheumatism stasis syndrome animal model.

METHODThe rat migraine rheumatism stasis syndrome animal model was established through rheumatism stimulation with manual climate box, 5-HT reduction caused by reserpine and local cerebral vasospasm. General vital signs (activity, weight, eye gum, hair, feeding, excrement), head scratch frequency and image collection were observed to analyze the changes in biological signs of stasis syndrome (tongue image RGB), thrombin and serotonin of model rats.

RESULTThe reserpine group and the reserpine plus rheumatism model group showed significant reduction in blood coagulation time, pain threshold and 5-HT content in blood and brain (P < 0.01); the reserpine plus rheumatism model group showed an increase in eye gum and decreases in activity, feeding, with thin sloppy stool. According to the tough RGB values, the control group showed light red toughs, the reserpine group showed dark purple toughs, the reserpine plus rheumatism model group showed gray toughs, with notable differences in tough RGB values in all three group.

CONCLUSIONThe rheumatism stimulation with manual climate box, 5-HT reduction caused by reserpine and local cerebral vasospasm can be used to induce the migraine rheumatism stasis syndrome animal model, but its modeling assessment method and process shall be further improved.

Animals ; Blood Circulation ; Diagnosis, Differential ; Disease Models, Animal ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Migraine Disorders ; diagnosis ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Rheumatic Diseases ; diagnosis ; physiopathology

OBJECTIVETo observe and evaluate the clinical effect of acupuncture at "Siguan" combined with the Gallbladder Meridian acupoints on migraine.

METHODSWith randomized controlled trial design, 87 patients were randomly divided into an observation group (42 cases) and a control group (45 cases). The observation group was treated with acupuncture at "Siguan" including Hegu (LI 4) and Taichong (LR 3), combined with the Gallbladder Meridian acupoints including Fengchi (GB 20), Shuaigu (GB 8), Qiuxu (GB 40) and Zulinqi (GB 41), while the control group was treated with acupuncture at the Gallbladder Meridian acupoints, including Fengchi (GB 20), Shuaigu (GB 8), Qiuxu (GB 40), Zulinqi (GB 41), Yanglingquan (GB 34) and Hanyan (GB 4). The treatment was given every other day in two groups, 3 times per week for totally 6 weeks. The migraine intensity, migraine frequency and lasting time of each migraine were observed before and after treatment, and 3-month follow-up was performed after treatment. The clinical efficacy in two groups was evaluated.

RESULTSCompared with those before treatment, the migraine intensity, frequency and lasting time were all reduced significantly after treatment in the two groups (all P<0.01), which were more obvious in the observation group (all P<0.05). At the end of the treatment, the total effective rate was 95.2% (40/42) in the observation group and 80.0% (36/45) in the control group, which had statistical difference (P<0.05). After 3-month follow-up, the total effective rate was 88.1% (37/42) in the observation group and 75.6% (34/45) in the control group, which had no statistical difference (P>0.05).

CONCLUSIONThe "Siguan" combined with the Gallbladder Meridian acupoints could significantly relieve the migraine intensity, frequency and lasting time, and its improvement of symptoms and short-term efficacy are superior to those of the Gallbladder Meridian acupoints alone.

Acupuncture Points ; Acupuncture Therapy ; Adolescent ; Adult ; Female ; Gallbladder ; physiopathology ; Humans ; Male ; Meridians ; Middle Aged ; Migraine Disorders ; physiopathology ; therapy ; Young Adult

Acupuncture Points ; Acupuncture Therapy ; Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Migraine Disorders ; physiopathology ; therapy ; Occipital Bone ; physiopathology ; Young Adult