ChiCTR-RRC-17014152.

Objective To explore the efficacy of botulinum toxin type A (BTX-A) therapy in relieving anxiety and depression in patients with hemifacial spasm (HFS) and benign essential blepharospasm (BEB). Patients and method Ninety idiopathic HFS patients and 90 BEB patients were enrolled. The anxiety and depression status were evaluated by self-rating anxiety scale (SAS) and self-rating depression scale (SDS), respectively, before and after the injection of BTX-A. Results Before treatment, the SAS and SDS scores of HFS patients were 41.25±6.35 and 42.25±7.57, respectively. The SAS scores were 40.17±8.36 for males and 43.56±6.10 for females ( P =0.031). The SDS scores were 40.25±6.46 for males and 45.48±7.31 for females ( P =0.008). After treatment, the SAS and SDS scores were 30.12±4.35 and 30.58±4.89, respectively. There was a significant difference in the SAS and SDS scores before and after treatment. Before treatment, the SAS scores of male and female BEB patients were 56.45±8.75 and 60.89±9.11, respectively, and the SDS scores of male and female BEB patients were 57.90±7.93 and 60.12±8.35, respectively. After treatment, the SAS score was 38.17±3.67 and the SDS score was 38.12±4.15, with a significant difference in before and after treatment scores. Conclusion In HFS and BEB, especially in female patients, there is an association with anxiety and depression. BTX-A can improve the symptoms of anxiety and depression.

Background The incidence of migraines is higher among individuals with epilepsy than in healthy individuals, and these two diseases are thought to shared pathophysiological mechanisms. Excitation/inhibition imbalance plays an essential role in the comorbidity of epilepsy and migraine. Microglial activation is crucial for abnormal neuronal signal transmission. However, it remains unclear whether and how microglia are activated and their role in comorbidities after being activated. This study aimed to explore the characteristics and mechanism of microglial activation after seizures and their effect on migraine. Methods Model rats of status epilepticus (SE) induced by intraperitoneal injection of lithium chloride (LiCl)-pilocarpine and migraine induced by repeated dural injections of inflammatory soup (IS) were generated, and molecular and histopathologic evidence of the microglial activation targets of fractalkine (FKN) signalling were examined. HT22-BV2 transwell coculture assays were used to explore the interaction between neurons and microglia. LPS (a microglial agonist) and FKN stimulation of BV2 microglial cells were used to evaluate changes in BDNF levels after microglial activation. Results Microglia were specifically hyperplastic and activated in the temporal lobe cortex, thalamus, and spinal trigeminal nucleus caudalis (sp5c), accompanied by the upregulation of FKN and CX3CR1 four days after seizures. Moreover, SE-induced increases in nociceptive behaviour and FKN/CX3CR1 axis expression in migraine model rats. AZD8797 (a CX3CR1 inhibitor) prevented the worsening of hyperalgesia and microglial activation in migraine model rats after seizures, while FKN infusion in migraine model rats exacerbated hyperalgesia and microglial activation associated with BDNF-Trkb signalling. Furthermore, in neuron-microglia cocultures, microglial activation and FKN/CX3CR1/BDNF/iba1 expression were increased compared with those in microglial cultures alone. Activating microglia with LPS and FKN increased BDNF synthesis in BV2 microglia. Conclusions Our results indicated that epilepsy facilitated migraine through FKN/CX3CR1 axis-mediated microglial activation in the cortex/thalamus/sp5c, which was accompanied by BDNF release. Blocking the FKN/CX3CR1 axis and microglial activation are potential therapeutic strategies for preventing and treating migraine in patients with epilepsy.

Migraine is the second most common form of headache disorder and the second leading cause of disability worldwide. Cognitive symptoms ranked second resulting in migraine-related disability, after pain. P2X7 receptor (P2X7R) was recently shown to be involved in hyperalgesia in migraine. However, the role of P2X7R in migraine-related cognitive impairment is still ill-defined. The aim of this study was to explore the molecular mechanisms underlying migraine-related cognitive impairment and the role of P2X7R in it. Here we used a well-established mouse model of migraine that triggered migraine attacks by application of inflammatory soup (IS) to the dura. Our results showed that repeated dural IS stimulation triggered upregulation of P2X7R, activation of NLRP3 inflammasome, release of proinflammatory cytokines (IL-1β and IL-18) and activation of pyroptotic cell death pathway. Gliosis (microgliosis and astrogliosis), neuronal loss and cognitive impairment also occurred in the IS-induced migraine model. No significant apoptosis or whiter matter damage was observed following IS-induced migraine attacks. These pathological changes occurred mainly in the cerebral cortex and to a less extent in the hippocampus, all of which can be prevented by pretreatment with a specific P2X7R antagonist Brilliant Blue G (BBG). Moreover, BBG can alleviate cognitive impairment following dural IS stimulation. These results identified P2X7R as a key contributor to migraine-related cognitive impairment and may represent a potential therapeutic target for mitigating cognitive impairment in migraine.

The nature and magnitude of nocebo responses in primary headache disorders are still unknown. To assess the distribution and possible predictors of nocebo responses in primary headache treatments, databases, including PubMed, EMBASE, and Cochrane Library were searched from 1988 to December 31, 2020, for parallel‐group, double‐blind, randomized placebo‐controlled trials of pharmacologic treatments of primary headaches. The nocebo responses were calculated using a random effects meta‐analysis model. Subgroup and metaregression analyses were performed to determine the associations of study design and demographic characteristics with nocebo responses. A total of 178 randomized controlled trials that satisfied the inclusion criteria were included. Prophylactic treatments elicited stronger nocebo responses than acute treatments. The majority of nocebo adverse events were mild to moderate in severity, with the nervous and digestive systems being the most commonly affected. There was a strong correlation between the active medication and control groups in terms of adverse events, both quantitatively and qualitatively. Long treatment duration, a high proportion of subjects receiving active medications, multicenter design, North America, high body mass index, women, previous treatment experiences, and a high proportion of patients with migraine headache with aura were all found to be significant positive predictors of nocebo responses, whereas the year of publication was found to be inversely related to them. Nocebo effects should be noticed for their contribution to discontinuation of or lack of adherence to active treatments. Clarifying these nocebo‐related risk factors can aid in their clinical prevention and management.