Correlation analysis of heart rate variations and glucose fluctuations during sleep.

OBJECTIVE: The body's glucose concentration is influenced by carbohydrate intake, insulin-induced carbohydrate reduction, and hepatic glycogen breakdown induced by stress hormones. This study investigated the potential of employing glucose fluctuations as a measure of stress by examining the relationship between heart rate variability (HRV) data and glucose levels during sleep in healthy subjects. METHODS: In this cross-sectional study, a chest-worn electrocardiogram (ECG) and continuous glucose monitoring device (CGM) were respectively used to monitor the heart rate intervals and glucose fluctuations of five subjects (two males, three females) during sleep. A time-series correlation analysis was performed on the HRV data extracted from heart rate intervals and the corresponding glucose fluctuation data. RESULTS: The time-series analysis of ECG and CGM data collected from subjects during sleep (n = 25 nights) revealed a moderate negative correlation between glucose levels and HRV, with a cross-correlation coefficient of r = -0.453. CONCLUSION: Similar to HRV, changes in stress levels can be detected by observing glucose fluctuations, particularly during sleep when the impact of food intake can be eliminated. Our findings highlight a significant correlation between glucose levels and HRV, indicating that glucose fluctuations can be used as an indicator of autonomic nervous system activity in an exploratory study.

[Acupuncture; as a valuable tool for headache].

Acupuncture is known as the effective tool for headache, but the mechanism of the effect is unknown. We already revealed the acupuncture effect in the clinical team of headache center in Keio University Hospital. Therefore, we tried to establish the animal model for elucidation of mechanism of acupuncture effect in the pathophysiology of headache. Resent study, we reveal the threshold-reduction of the genesis of the cortical spreading depression (CSD; thought as the trigger of migraine attack) during the trigeminal nerve stimulation. This result suggests that, the somatosensory stimulation may influence the occurrence and severity of the pathogenesis of migraine. Furthermore, we assume that our result may lead to the underlying mechanism of acupuncture effect.

Reduction of TRPV1 expression in the trigeminal system by botulinum neurotoxin type-A.

Botulinum neurotoxin type-A (BoNT-A) is clinically used for patients with pain disorders and dystonia. The precise mechanism whereby BoNT-A controls pain remains elusive. Here, we studied how BoNT-A affects the expression of the transient receptor potential vanilloid subfamily member 1 (TRPV1), a cation channel critically implicated in nociception, in the trigeminal system. Histological studies revealed that subcutaneous BoNT-A injection (0.25, 0.5, or 5 ng/kg) into the face targeted the ophthalmic division of trigeminal ganglion (TG) neurons and decreased TRPV1-immunoreactive neurons in the TG and TRPV1-immunoreactive fibers in rat trigeminal terminals. Of note, TG neurons that received projections from the dura mater, a principal site of headache generation, had reduced TRPV1 expression. BoNT-A-induced cleavage of SNAP25 (synaptosomal-associated protein of 25-kDa) in the TG became obvious 2 days after BoNT-A administration and persisted for at least 14 days. Quantitative real-time RT-PCR (reverse transcription-polymerase chain reaction) data indicated that the TRPV1-decreasing effects of BoNT-A were not mediated by transcriptional downregulation. By employing a surface protein biotin-labeling assay, we demonstrated that BoNT-A inhibited TRPV1 trafficking to the plasma membrane in primary TG neurons. Moreover, Y200F-mutated TRPV1, which is incapable of trafficking to the plasma membrane, was expressed in PC12 cells by transfection, and pharmacological studies revealed that TRPV1 in the cytoplasm was more predisposed to proteasome-mediated proteolysis than plasma membrane-located TRPV1. We conclude that the mechanism by which BoNT-A reduces TRPV1 expression involves the inhibition of TRPV1 plasma membrane trafficking and proteasome-mediated degradation in the cytoplasm. This paradigm seems to explain how BoNT-A alleviates TRPV1-mediated pain. Our data reveal a likely molecular mechanism whereby BoNT-A treatment reduces TRPV1 expression in the trigeminal system and provide important clues to novel therapeutic measures for ameliorating craniofacial pain.

Alterations in microglia and astrocytes in the trigeminal nucleus caudalis by repetitive TRPV1 stimulation on the trigeminal nociceptors.

TRPV1 is a nonselective cation channel in nociceptors. TRPV1 stimulation has been shown to lead to the activation of microglia and astrocytes in the dorsal horn of the spinal cord. However, information on the effect of TRPV1 stimulation on glial activation in the trigeminal nucleus caudalis (TNC) is lacking. Here, we stimulated TRPV1 in the trigeminal afferents by a repetitive injection of 10 mmol/l capsaicin into the whisker pad for 2 days (d2 group), 4 days (d4 group), or 6 days (d6 group). As a control (c group), the vehicle was injected for 2 days. Anti-Iba1 and anti-glial fibrillary acidic protein antibodies were used to immunostain microglia and astrocytes in the TNC, respectively. The ratio of the cross-sectional area immunoreactive for Iba1 to the entire area of the TNC was increased in the d2 group compared with the c group on the injected side. Microglia were recruited to the superficial layers of the TNC. The numbers of microglia were reduced in the d4 group and the d6 group compared with the d2 group. The ratio of the cross-sectional area immunoreactive for glial fibrillary acidic protein to the entire TNC showed a significant increase in d2 group and the d4 group compared with the c group on the injected side. Behavioral analysis indicated that mechanical allodynia began to develop after 2 days of capsaicin treatment and persisted for at least 6 days after the onset of the repetitive capsaicin injection. These data indicate that TRPV1 stimulation activates the microglia and astrocytes in temporally distinct ways and that the development of mechanical allodynia is independent of such glial activation.