NO up-regulates migraine-related CGRP via activation of an Akt/GSK-3ß/NF-κB signaling cascade in trigeminal ganglion neurons.

The release of the neuropeptide CGRP from the trigeminal ganglion neurons (TGNs) plays a central role in migraine. Whereas CGRP can activate NO release from ganglionic glial cells, NO in turn enhances CGRP release. However, it remains unclear how NO promotes CGRP release. Here, we report that the NO donor SNAP triggered CGRP release from cultured primary TGNs. This event was associated with GSK-3ß activation and Akt inactivation. Immunofluorescent staining revealed that GSK-3ß primarily located in neurons. Furthermore, GSK-3ß inhibition resulted in a marked reduction in expression of CGRP as well as other migraine-related factors, including substance P, cholecystokinin, and prostaglandin E2. Last, exposure to SNAP also activated NF-κB, while NF-κB inhibition prevented the induction of CGRP by SNAP. Interestingly, this event was blocked by GSK-3ß inhibition, in association with inhibition of NF-κB/p65 expression and nuclear translocation. Together, these findings argue that NO could stimulate TGNs to release of CGRP as well as other migraine-related factors, likely by activating GSK-3ß, providing a novel mechanism underlying a potential feed-forward loop between NO and CGRP in migraine. They also raise a possibility that GSK-3ß might act to trigger migraine through activation of NF-κB, suggesting a link between neuroinflammation and migraine.

Pacemaker implantation for treating migraine-like headache secondary to cardiac arrhythmia: A case report.

RATIONALE: Co-occurrence of headache and arrhythmia is not rare. However, their causal relationship remains unclear. Here, we described a case of migraine-like headache relieving with pacemaker implantation. Our case study indicates that arrhythmia is causal for migraine-like headache, which, to our knowledge, has never been reported. PATIENT CONCERNS: A 63-year-old woman patient suffered from paroxysmal headache with a visual aura presenting like migraine for 2 years. No ophthalmic or neurological disorder was found, but cardiac examination detected bradycardia, which was confirmed by 24-hour dynamic electrocardiogram (DCG) revealing sinus bradycardia mixed with ventricular premature beats and supraventricular tachycardia. Transcranial doppler (TCD) detected an equal echo flat plaque on the anterolateral wall of the common carotid artery (CA) bifurcation. DIAGNOSIS: Migraine-like headaches secondary to arrhythmia. INTERVENTIONS: The patient underwent pacemaker implantation. OUTCOMES: Both visual aura and headache were resolved following pacemaker implantation. LESSONS: To the best of the authors' knowledge, we are the first to report migraine-like headache as a secondary symptom of arrhythmia. Arrhythmia may aggravate insufficient blood supply to the brain due to CA lesion and induce a migraine-like headache. This case study indicated that pacemaker implantation could be a fundamental treatment for migraine-like headaches caused by cardiac arrhythmia.

A new variant nummular headache: large diameter accompanied with bitrigeminal hyperalgesia and successful treatment with carbamazepine.

Nummular headache (NH) is defined as a focal head pain that is exclusively felt in a small area, which is typically 1-6 cm in diameter. Neurological examinations are normal in all patients, but this report describes a new variant. A patient was identified who presented with focal head pain that was approximately 8 cm in diameter and bitrigeminal hyperalgesia on neurological examination. Treatment with carbamazepine provided significant analgesic relief in terms of both the frequency and intensity of pain. The findings enlarge the clinical diversity of this headache disorder. The pathogenic mechanisms of NH may be similar to trigeminal neuralgia in particular patients.

Influence of evoked HSP70 expression on hearing function of the cochlea in guinea pigs.

OBJECTIVE: To investigate the effect of evoked heat shock protein 70 (HSP70) expression on the hearing function of the cochlea in guinea pigs. METHODS: Guinea pigs were divided into pre-exposure group (pre-treated with white noise exposure at 100 dB SPL for 45 min) and none pre-exposure group. Auditory brainstem response (ABR) thresholds were recorded at 12, 60 and 108 h after the animals in both groups were exposed to loud white noise (125 dB SPL, 90 min). RESULTS: HSP70 expression was evoked by pre-treatment with white noise (100 dB SPL, 45 min). There was no significant difference of ABR thresholds between the 2 groups (P>0.05) at 12 h after exposure to loud noise, while ABR thresholds became lower in pre-exposure group than in none pre-exposure group (P<0.01) at both 60 and 108 h. In the pre-exposure group, ABR thresholds at 108 h were significantly lower than that measured at 60 h (P<0.05), but which was not the case in none pre-exposure group. CONCLUSION: HSP70 expression induced by pre-exposure to noise protects the hearing function of the cochlea in guinea pigs.