Scientific reports
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Common chemotherapeutic agents such as oxaliplatin often cause neuropathic pain during cancer treatment in patients. Such neuropathic pain is difficult to treat and responds poorly to common analgesics, which represents a challenging clinical issue. Corydalis yanhusuo is an old traditional Chinese medicine with demonstrated analgesic efficacy in humans. ⋯ In addition, we found that the anti-hyperalgesic effect of l-THP was significantly blocked by a dopamine D1 receptor antagonist SCH23390 (0.02 mg/kg), suggesting a dopamine D1 receptor mechanism. In contrast, l-THP did not significantly alter the general locomotor activity in mice at the dose that produced significant anti-hyperalgesic action. In summary, this study reported that l-THP possesses robust analgesic efficacy in mice with neuropathic pain and may be a useful analgesic in the management of neuropathic pain.
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Meta Analysis
Decompressive craniectomy for the treatment of malignant infarction of the middle cerebral artery.
Early decompressive craniectomy (DC) has been shown to reduce mortality in malignant middle cerebral artery (MCA) infarction, whereas efficacy of DC on functional outcome is inconclusive. Here, we performed a meta-analysis to estimate the effects of DC on malignant MCA infarction and investigated whether age of patients and timing of surgery influenced the efficacy. We systematically searched PubMed, Medline, Embase, Cochrane library, Web of Science update to June 2014. ⋯ In the subgroup analysis stratified by age, early DC improved outcome both in younger and older patients. However, later DC (after 48h after stroke onset) might not have a benefit effect on lowering mortality or improving outcome in patients with malignant infarction. Together, this study suggested that decompressive surgery undertaken within 48 h reduced mortality and increased the number of patients with a favourable outcome in patients with malignant MCA infarction.
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Alzheimer's disease (AD) is a lethal progressive neurological disorder affecting the memory. Recently, US Food and Drug Administration mitigated the standard for drug approval, allowing symptomatic drugs that only improve cognitive deficits to be allowed to accelerate on to clinical trials. Our study focuses on taurine, an endogenous amino acid found in high concentrations in humans. ⋯ Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages.
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The composition of the postsynaptic ionotropic receptors that receive presynaptically released transmitter is critical not only for transducing and integrating electrical signals but also for coordinating downstream biochemical signaling pathways. At glutamatergic synapses in the adult CNS an overwhelming body of evidence indicates that the NMDA receptor (NMDAR) component of synaptic responses is dominated by NMDARs containing the GluN2A subunit, while NMDARs containing GluN2B, GluN2C, or GluN2D play minor roles in synaptic transmission. Here, we discovered NMDAR-mediated synaptic responses with characteristics not described elsewhere in the adult CNS. ⋯ Strikingly, the charge transfer mediated by GluN2D far exceeds that of GluN2A and is comparable to that of GluN2B. Lamina I forms a distinct output pathway from the spinal pain processing network to the pain networks in the brain. The GluN2D-mediated synaptic responses we have discovered in lamina I neurons provide the molecular underpinning for slow, prolonged and feedforward amplification that is a fundamental characteristic of pain.
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This study assessed the potential antinociceptive effects of liquiritigenin, a plant-derived compound with transient receptor potential melastatin 3 blocking activity in a rat model of persistent neuropathic pain. Chronic constriction injury (CCI) to the sciatic nerve was induced in male Sprague-Dawley rats to model human peripheral neuropathic pain. Liquiritigenin (1, 3, or 9 mg/kg) was administered intraperitoneally to examine the effects on mechanical, thermal, and cold hyperalgesia using the von Frey test, plantar test, and cold plate test, respectively. ⋯ In addition, daily repeated treatment with liquiritigenin did not demonstrate significant antinociceptive tolerance in the measures of hyperalgesia. Within the doses studied, liquiritigenin did not significantly affect motor performance. These results suggest that liquiritigenin may be potentially useful novel treatments for neuropathic pain.