A migraine is a disabling neurovascular disorder characterized by a unilateral throbbing headache that lasts from 4 to 72 h. The headache is often accompanied by nausea, vomiting, phonophobia and photophobia, and may be worsened by physical exercise. The trigeminovascular system (TVS) is speculated to have an important role in migraines, although the pathophysiology of this disorder remains to be elucidated. Trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis (TNC) are important components of the TVS. Several clinical cases have provided evidence for the involvement of the brainstem in migraine initiation. Electrical stimulation of the trigeminal ganglion (ESTG) in rats can activate TVS during a migraine attack. Calcitonin gene-related peptide (CGRP) is an important vasoactive compound produced following TVS activation. Numerous studies have revealed that adenosine and its receptors have an important role in pain transmission and regulation process. However, only a few studies have examined whether adenosine A2a receptor (A2aR) and adenosine A1 receptor (A1R) are involved in migraine and nociceptive pathways. In the present study, CGRP, A2aR and A1R expression levels were detected in the TG and TNC of ESTG models through reverse transcription-quantitative polymerase chain reaction and western blot analysis. Tianshu capsule (TSC), a type of Chinese medicine, was also used in the ESTG rat models to examine its influence on the three proteins. Results demonstrated that CGRP, A2aR and A1R mediated pain transmission and the regulation process during migraine and the expression of the three proteins was regulated by TSC.

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A/J and C57BL/6 J (B6) mice share a mutation in Cdh23 (ahl allele) and are characterized by age-related hearing loss. However, hearing loss occurs much earlier in A/J mice at about four weeks of age. Recent study has revealed that a mutation in citrate synthase (Cs) is one of the main contributors, but the mechanism is largely unknown. In the present study, we showed that A/J mice displayed more severe degeneration of hair cells, spiral ganglion neurons, and stria vascularis in the cochleae compared with B6 mice. Moreover, messenger RNA accumulation levels of caspase-3 and caspase-9 in the inner ears of A/J mice were significantly higher than those in B6 mice at 2 and 8 weeks of age. Immunohistochemistry localized caspase-3 expression mainly to the hair cells, spiral ganglion neurons, and stria vascularis in cochleae. In vitro transfection with Cs short hairpin RNA (shRNA) alone or cotransfection with Cs shRNA and Cdh23 shRNA significantly increased the levels of caspase-3 in an inner ear cell line (HEI-OC1). Finally, a pan-caspase inhibitor Z-VAD-FMK could preserve the hearing of A/J mice by lowering about 15 decibels of the sound pressure level for the auditory-evoked brainstem response thresholds. In conclusion, our results suggest that caspase-mediated apoptosis in the cochleae, which may be related to a Cs mutation, contributes to the early onset of hearing loss in A/J mice.