Midbrain enkephalin expression in a rat migraine model following intragastric scorpion powder administration

Scorpion has strong analgesic effects, but its analgesic mechanisms remain unclear. This study investigated the effects of scorpion powder on enkephalin expression in the midbrain of rats with nitroglycerin-induced migraine at mRNA and protein levels. Results confirmed that migraine rat abnormal behavior was significantly improved, and proenkephalin mRNA expression was significantly increased following treatment with scorpion. The number of methionine-enkephalin- positive cells in the migraine rats following treatment with scorpion was significantly increased, but no significant difference in the number of leucine-enkephalin-positive cells was detectable compared with migraine and normal rats. Taken together, these results show that scorpion exerts potentially beneficial effects by promoting enkephalin expression in nitroglycerin-induced migraine rats.

Rizatriptan benzoate influences the endogenous pain modulatory system in a rat model of migraine

The present study utilized a nitroglycerin-induced rat model of migraine to detect the effects of rizatriptan benzoate on proenkephalin and substance P gene expression in the midbrain using real-time quantitative polymerase chain reaction and investigate whether rizatriptan benzoate can regulate the endogenous pain modulatory system. The results showed that rizatriptan benzoate significantly reduced expression of the mRNAs for proenkephalin and substance P. Rizatriptan benzoate may inhibit the analgesic effect of the endogenous pain modulatory system.

Therapeutic effects and safety of olcegepant and telcagepant for migraine A meta-analysis

OBJECTIVE： To evaluate the therapeutic effects and adverse reactions of olcegepant and telcagepant for the treatment of migraine. DATA RETRIEVAL： We identified studies using Medline （1966-01/2012-06）, PubMed （1966-01/2012-06）, Scopus （1980-01/2012-06）, Cochrane Central Register of Controlled Trials （1980-01/2012-06） and China National Knowledge Infrastructure （1980-01/2012-06）. SELECTION CRITERIA： The included studies were double-blind, randomized and placebo-controlled trials of olcegepant or telcagepant for the treatment of single acute migraine in patients with or without aura. Adverse reaction data were also included. Two independent investigators performed quality evaluation and data extraction using Jadad scoring. Meta-analyses were undertaken using RevMan 5.0.25 software. MAIN OUTCOME MEASURES： Pain relief rate, pain-free rate, and incidence of adverse reactions were measured in patients 2 and 24 hours after injection of olcegepant and oral teicagepant. RESULTS： Six randomized, controlled trials were included. Meta-analysis demonstrated that compared with placebo, the pain relief rate （odds ratio, OR = 5.21, 95% confidence interval, CI： 1.91-14.2, P 〈 0.01） and pain-free rate （OR = 31.11, 95% Ch 3.80-254.98, P 〈 0.01） significantly increased 2 hours after 2.5 mg/d olcegepant treatment. Pain relief rate and pain-free rate 2 and 24 hours after treatment with telcagepant 150 mg/d and 300 mg/d were superior to placebo （P 〈 0.01）. Moreover, the remission rate of unrelenting headache was higher after 24 hours of 300 mg/d telcagepant treatment compared with 150 mg/d （OR = 0.78, 95% Ch 0.62-0.97, P 〈 0.05）. The incidence of adverse reactions with olcegepant was not significantly greater than placebo （P = 0.28） but within 48 hours of administration of telcagepant 300 mg/d, the incidence of adverse reactions was higher than placebo （OR = 1.21,95% Ch 1.04-1.42, P 〈 0.01）. Few studies have compared the therapeutic effects of olcegepant and telcagepant. CONCLUSION： The calcitonin-gene-related peptide receptor antagonists olcegepant and telcagepant have shown good therapeutic effects in the treatment of migraine. Moreover, the incidence of adverse reactions compares favorably with placebo, although liver transaminases may become elevated after long-term use.

Effects of Toutongning capsule on enkephalin expression in a rat migraine headache model

Toutongning capsule is used for the treatment of migraine headaches, and has yielded therapeutically beneficial effects. However, whether Toutongning capsule exerts its effects via endogenous opioid peptides remains poorly understood. This study investigated the effects of Toutongning capsule on enkephalin expression in the midbrain of rats with nitroglycerin-induced migraine headache at the mRNA and protein levels. Results confirmed that proenkephalin mRNA levels were significantly upregulated following treatment with Toutongning capsule. The numbers methionine-enkephalin and leucine-enkephalin-positive cells were significantly greater in the migraine headache rats following treatment with Toutongning capsule compared with the model group. Taken together, these results show that Toutongning capsule exerts potentially beneficial effects by promoting enkephalin expression in nitroglycerin-induced migraine headache rats.

Magnesium effects on behavior and substance P mRNA expression in the midbrain of a rat migraine model

BACKGROUND： Substance P participates in pain transmission and modulation, suggesting a close association with migraine headaches. The clinical application of magnesium has been effective in treating migraines, and the action mechanisms underlying migraines correlate with substance P expression. OBJECTIVE： To analyze different magnesium doses on behavior and substance P mRNA expression in the midbrain of a rat migraine model, and to determine the action pathway of migraine treatment using magnesium. DESIGN, TIME AND SETTING： A completely randomized, controlled, animal experiment was performed at the Experimental Animal Center and Central Laboratory in the Second Hospital of Jilin University between 2007 and 2008. MATERIALS： Magnesium sulfate （25%） was supplied by Tianjin Pharmaceutical Jiaozuo, China. Nitroglycerin was provided by Shanxi Kangbao Biological, China. Substance P primer sequence was synthesized by TaKaRa Biotechnology （Dalian）, China. METHODS： A total of 36 healthy, adult, Wistar rats were randomly assigned to 6 groups： control, migraine, low- and high-dose magnesium sulfate treated, and low- and high-dose magnesium sulfate control, with 6 rats in each group. Migraines were induced by subcutaneous injection of 10 mg/kg nitroglycerin in the migraine and low- and high-dose magnesium sulfate treated groups, and 2 mL/kg physiological saline was administered to rats in the control and low- and high-dose of magnesium sulfate control groups. Five minutes following administration, rats in low-dose groups were intraperitoneally injected with 100 mg/kg magnesium sulfate, while those in high-dose groups were injected with 300 mg/kg magnesium sulfate. No interventions were administered to the control and migraine groups. MAIN OUTCOME MEASURES： At 2 hours after nitroglycerin injection, substance P mRNA expression in the rat midbrain was measured by real-time quantitative polymerase chain reaction. At 60-90 minutes after nitroglycerin injection, behavioral changes of pain were analyzed in the experimental rats. RESULTS： The migraine group exhibited significantly lower levels of substance P mRNA expression compared with the control group （P 〈 0.05）. Following magnesium sulfate injection, substance P mRNA expression increased, compared with the migraine and control groups （P 〈 0.05）. In the low- and high-dose magnesium sulfate treated groups, pain behavior was remarkably ameliorated, compared with the migraine group （P 〈 0.05）, particularly with the high-dose injection （P 〈 0.05）. CONCLUSION： Magnesium relieved pain behaviors in a rat migraine model in a dose-dependent manner, and the therapeutic effect was achieved in conjunction with increased substance P expression in the midbrain.

Meta-analysis of efficacy of topiramate in migraine prophylaxis

OBJECTIVE：To evaluate the treatment effects and safety of topiramate in migraine prophylaxis. DATA RETRIEVAL：We searched the Medline database,EMbase,Cochrane Library and China National Knowledge Infrastructure database for articles published between January 1995 and May 2011,using the key words＂migraine＂,＂topiramate＂,and＂prophylaxis＂. SELECTION CRITERIA：We selected randomized controlled trials of migraine patients,in which the experimental group was orally administered topiramate,and the control group was given placebo. Odds ratios（ORs）and mean differences（MDs）were calculated using a fixed effects model/random effects model.Quality evaluation and data extraction were performed independently by two researchers utilizing RevMan 5.0 software. MAIN OUTCOME MEASURES：Efficacy was recorded as the responder rate（response defined as at least a 50%reduction in average monthly migraine frequency）and change in mean monthly number of migraine days.Adverse events were recorded as the number of subjects exhibiting at least one adverse event. RESULTS：Eight randomized controlled trials were found to be appropriate,and had available data. The meta-analysis results revealed that topiramate（100 or 200 mg/d）was more effective than placebo in responder rate（OR=2.97,95%confidence interval（CI）：2.17-4.08,P〈0.01;OR=2.35, 95%CI：1.77-3.12,P〈0.01）.Topiramate（100 mg/d）was more effective than placebo in terms of the change in mean monthly migraine days（MD：-1.14,95%CI：-1.69 to-0.59,P〈0.01）.The total incidence rate of adverse events for topiramate was higher than in the placebo group（P〈0.01）,but most adverse events were mild to moderate. CONCLUSION：Overall,topiramate obtained good outcomes and safety in migraine prophylaxis.

A case of thalamic hemorrhage-induced diaschisis

Diaschisis refers to a disturbance （inhibition or facilitation） of function in an area remote from the site of a primary brain lesion. Previous studies have confirmed that regional cerebral blood flow and metabolism are noticeably decreased in an infarct region. Transient excessive perfusion appears in the ischemic penumbra, and diaschisis occurs in an area remote from the lesion site, showing decreased regional cerebral blood flow and metabolism. Mirror diaschisis refers to a decrease in oxygen metabolism and blood flow in the ＂mirror image area＂ to the infarct regions in the contralateral hemisphere. In this study, a patient with right thalamic hemorrhage was affected with right arm and leg numbness. At 4 months before onset, magnetic resonance imaging of the head demonstrated lacunar infarcts in the left thalamus; therefore the right arm and leg numbness was not associated with lacunar infarcts in the left thalamus. At 8 days following onset, magnetic resonance imaging reexamination did not reveal the focus that could induce right arm and leg numbness and weakness. Thus, it is suggested in this study that the onset of this disease can be explained by mirror diaschisis. That is, right thalamic hemorrhage leads to decreased blood flow and metabolic disturbance in the contralateral thalamus, resulting in right arm and leg numbness.