Abstract
BackgroundMigraine is painful disease in which neurotransmitters related to pain transmission play an important role. Hejie Zhitong prescription (HJZT) has been used in the clinic as an effective prescription for the treatment of migraine for many years. Our team aimed to further explore its antimigraine mechanism based on previous research results and to explore the inhibitory effect of HJZT on the transmission of pain related to nitroglycerine (NTG)-induced migraine as well as the synergistic effect of HJZT with pentobarbital sodium on promoting sleep.MethodsSixty mice were randomly assigned to groups and received the corresponding interventions. Sleep latency and sleep time were recorded to calculate the incidence of sleep. Forty-eight Wistar rats were randomly assigned and administered an intervention corresponding to their group. Calcitonin gene-related peptide (CGRP), serotonin (5-HT), substance P (SP), and cholecystokinin (CCK) levels were measured using ELISAs. Levels of the cannabinoid receptor type 1 (CB1R) and cyclooxygenase-2 (COX-2) protein were assessed using immunohistochemistry. The expression of the CGRP and CCK mRNAs in the midbrain and trigeminal ganglion (TG) were measured using real-time quantitative PCR.ResultsHJZT promoted the occurrence of sleep in mice. HJZT downregulated COX-2 expression in the midbrain and TG of rats but upregulated the expression of the CB1R, and decreased the plasma level of the CGRP protein and expression of its mRNA in the midbrain and TG. It also downregulated the expression of the CCK mRNA in the midbrain and TG. The high-dose HJZT treatment increased plasma 5-HT levels, but did not induce changes in the plasma levels of the SP or CCK protein.ConclusionsHJZT exerts a synergistic effect with pentobarbital sodium on promoting sleep. As for anti-migraine, HJZT can inhibits the expression of nociceptive transmission-associated neurotransmitters, including 5-HT, CGRP and CCK, which may be related to its upregulation of CB1R and downregulation of COX-2.
Highlights
Migraine is painful disease in which neurotransmitters related to pain transmission play an important role
An increased emphasis has been placed on the role of the trigeminovascular system in connecting peripheral events with central consequences; trigeminal ganglion (TG) neurons provide the connection between the periphery by expressing the neuropeptide calcitonin gene-related peptide (CGRP) at high levels [10]
Migraine often occurs at the same time as insomnia, and treating insomnia may help relieve the main symptoms of migraine
Summary
Migraine is painful disease in which neurotransmitters related to pain transmission play an important role. Migraine is a common clinical chronic neurovascular disease with paroxysmal and recurrent characters. It reduces patients’ quality of life and increases the economic burden [1].As the sixth most disabling disease worldwide, it has substantially affected humans for centuries [2, 3]. Prophylactic treatment may reduce the frequency of pain, improve the quality of life of patients and prevent progression of the disease to chronic migraine [5],with which insomnia commonly co-occurs [6].As the study of migraine has progressively intensified, the hypotheses of its pathological mechanism have developed from a purely vascular to a neurovascular hypothesis, but the site of initial activation of the migraine process is uncertain. An increased emphasis has been placed on the role of the trigeminovascular system in connecting peripheral events with central consequences; trigeminal ganglion (TG) neurons provide the connection between the periphery by expressing the neuropeptide calcitonin gene-related peptide (CGRP) at high levels [10]
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