Quercetin alleviates thermal and cold hyperalgesia in a rat neuropathic pain model by inhibiting Toll-like receptor signaling.

Neuropathic pain is caused by lesion or disease of the nervous system, which results in abnormal spontaneous and evoked pain. It's common in clinical practice and greatly impairs the life quality of patients, but the effective treatment is still lacking. In this study, we aimed to explore the effect of quercetin (QUE) on neuropathic pain and the underlying mechanisms. Spinal nerve ligation (SNL) was performed in Sprague Dawley rats to establish the neuropathic pain model. Single or continuous oral administration of QUE after the operation or continuous administration before the operation was applied to evaluate the effects of QUE on SNL-induced thermal and cold hyperalgesia. Dorsal root ganglions from these rats were harvested to analyze the expression levels of some inflammatory mediators. Primary cultured astrocytes and HEK293 cells were used to further explore the downstream signaling pathways of QUE. Both single and continuous oral administration of QUE dose-dependently alleviated SNL-induced thermal and cold hyperalgesia. Pre-administration also attenuated neuropathic pain symptoms. Meanwhile, SNL-induced increase in protein or mRNA levels of some inflammatory mediators could be down-regulated by QUE treatment. Furthermore, QUE reduced the phosphorylation of TAK1, IKK and JNK2 in cultured astrocytes. Moreover, luciferase assay in HEK293 cells showed that QUE dose-dependently inhibited NF-κB activity only via TAK1. QUE exerts anti-inflammatory effects and alleviates neuropathic pain through the inhibition of Toll-like receptor signaling pathway. It could shed some light on the potential applications of QUE in chronic pain therapy.

[Effect of propofol on spinal cord apoptosis associated with aortic cross-clamping in rabbits].

OBJECTIVE: To investigate the effect and mechanism of propofol on the spinal cord apoptosis associated with aortic cross-clamping in rabbits. METHODS: Twenty-four rabbits were randomly divided into sham operation group (A), ischemia/reperfusion group (B) and propofol group (C). In group B and C, the infrarenal aorta was clamped for 40 minutes followed by 7 days reperfusion. Ten minutes before clamping, group C was given propofol 5 mg/kg intravenously and continued at a rate of 20 mg x kg(-1)x h(-1) until unclamping. The aorta was not clamped in group A. The plasma concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined at 10 minutes before clamping (C-10), before unclamping (C40), at 60 minutes (R60) and on the 7th day (R7 d) unclamping. Apoptotic spinal cord cells and expressions of Bax, Bcl-2 protein were measured by immunohistochemical technique. RESULTS: (1)The concentrations of MDA after ischemia and reperfusion in group B were increased significantly compared with C-10 and those in group A (P<0.05 or P<0.01), which in group C were significantly lower than those in group B (P<0.05), but not in group A. Changes in SOD activity were opposite to those in MDA contents in various groups. (2)The expressions of Bax protein in group B were significantly increased compared with those in group A (P<0.05), while the expression of Bcl-2 protein decreased. In group C, Bax protein expression was markedly lower than those in group B and higher than those in group A (P<0.01 and P<0.05), the expression of Bcl-2 was higher than those in groups B and A (both P<0.01). (3)The number of apoptosis cells in group B was much higher than that in group A, which in group C was much lower than that in group B, but higher than that in group A. (4)The ratio of paralysis in group C was significantly lower than that in group B with a high neurologic score (both P<0.01). CONCLUSION: Propofol can reduce the spinal cord apoptosis associated with aortic cross-clamping in rabbits. The possible mechanism is related to the effect of decreasing Bax expression, increasing Bcl-2 expression, and enhancing antioxidation.