地佐辛应用于瑞芬太尼静脉麻醉后患者的痛觉过敏观察

目的探析地佐辛对瑞芬太尼静脉麻醉术后患者疼痛过敏的影响，评价其镇痛的安全性以及有效性。方法选择腹腔镜下手术患者60例为研究对象，回顾性分析其临床资料。结果观察组患者要求进行镇痛距手术结束时间明显比对照组长（P〈0．05）；观察组患者在T1、T2、T3时点Ramsay评分明显优于对照组（P〈0．05），T3时点观察组VAS评分明显优于对照组（P〈0．05）；苏醒和拔管的时间、呼吸抑制、恶习呕吐等差异不具有统计学意义（P〉0．05）。结论地佐辛能有效的得到控制或者改善疼痛过敏，有效地减轻患者术后的疼痛感，安全性高。     

Experimental hypoglycemia is a human model of stress-induced hyperalgesia

Hypoglycemia is a physiological stress that leads to the release of stress hormones, such as catecholamines and glucocorticoids, and proinflammatory cytokines. These factors, in euglycemic animal models, are associated with stress-induced hyperalgesia. The primary aim of this study was to determine whether experimental hypoglycemia in humans would lead to a hyperalgesic state. In 2 separate 3-day admissions separated by 1 to 3 months, healthy study participants were exposed to two 2-hour euglycemic hyperinsulinemic clamps or two 2-hour hypoglycemic hyperinsulinemic clamps. Thermal quantitative sensory testing and thermal pain assessments were measured the day before and the day after euglycemia or hypoglycemia. In contrast to prior euglycemia exposure, prior hypoglycemia exposure resulted in enhanced pain sensitivity to hot and cold stimuli as well as enhanced temporal summation to repeated heat-pain stimuli. These findings suggest that prior exposure to hypoglycemia causes a state of enhanced pain sensitivity that is consistent with stress-induced hyperalgesia. This human model may provide a framework for hypothesis testing and targeted, mechanism-based pharmacological interventions to delineate the molecular basis of hyperalgesia and pain susceptibility.     

Dietary constituent genistein inhibits the hyperexcitability of trigeminal nociceptive neurons associated with mechanical hyperalgesia following orofacial inflammation

ObjectivesGenistein, a dietary constituent, modulates voltage-dependent and ligand-gated ionic channels, suggesting that it could also attenuate inflammatory hyperalgesia. However, the mechanism underlying how genistein affects inflammation-induced hyperexcitability of nociceptive neurons in vivo remains to be determined. The present study therefore investigated whether administration of genistein could attenuate the inflammation-induced hyperexcitability of trigeminal spinal nucleus caudalis (SpVc) neurons associated with mechanical hyperalgesia in vivo.MethodsInflammation was induced by injection of complete Freund's adjuvant into the whisker pad. The mechanical thresholds for escape behavior and electrophysiological single-unit recording of SpVc neurons responding to mechanical stimulation were then conducted in naïve rats, inflamed rats, and inflamed rats with genistein administered intraperitoneally.ResultsThe lowered mechanical threshold in the inflamed rats was returned to control level following administration of genistein for 2 days. The mean number of discharge frequencies of SpVc neurons in inflamed rats was significantly decreased after genistein administration with both non-noxious and noxious mechanical stimuli. The increased spontaneous discharges of SpVc neurons in inflamed rats were significantly decreased after genistein administration. Noxious pinch-evoked after-discharge frequency and occurrence in inflamed rats was also significantly diminished after genistein administration, and expansion of the receptive field was significantly returned to control levels in inflamed rats.ConclusionHerein, we present the first evidence that genistein attenuates hyperexcitability of SpVc neurons associated with inflammatory mechanical hyperalgesia. These findings suggest that genistein could be a potential therapeutic agent in complementary alternative medicine for the prevention of trigeminal inflammatory hyperalgesia.     

二甲基亚砜抑制吗啡诱导热痛觉过敏的实验研究

【摘要】 目的 观察二甲基亚砜(DMSO)对吗啡诱导的热痛觉过敏及其对脊髓背角肿瘤坏死因子(TNF-α)表达的影响。方法 32只SD大鼠随机分为4组,A组(生理盐水+吗啡组)、B组(10%DMSO 5 mL/kg+吗啡组),C组(10%DMSO 5 mL/kg+生理盐水组)和D组(生理盐水组)。各组大鼠分别每d3PM腹腔注射生理盐水或DMSO,30 min后皮下注射吗啡或生理盐水。观察注药前1 d,注药后3 d、6 d、10 d大鼠热刺激撤足潜伏期的变化及脊髓背角TNF?鄄α表达情况。结果 与注药前相比,A组注药后3 d开始热刺激撤足潜伏期缩短,10 d进一步缩短(P<0.01)。与A组比较,B组注药后6 d、10 d热刺激撤足潜伏期延长有统计学意义(P<0.01)。A组脊髓背角TNF?鄄α表达较其它组增高(P<0.01)。B组TNF?鄄α的表达较A组低,较D组高有统计学意义(P<0.01)。结论 DMSO可能通过抑制脊髓背角TNF?鄄α的产生而减轻吗啡诱导的热痛觉过敏。     

蛋白激酶Cα相互作用蛋白在瑞芬太尼痛觉过敏中的作用

背景 瑞芬太尼痛觉过敏是指应用瑞芬太尼所导致的机体对伤害性刺激的反应增强,其发生机制与N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体-蛋白激酶C (protein kmase C,PKC)通路介导的脊髓中枢敏化相关.蛋白激酶Cα相互作用蛋白(protein interacting withCαkinase,PICK1)是PKCα的靶蛋白之一,也是在PKCα和突触后膜受体蛋白间起重要作用的衔接蛋白. 目的 探讨PICK1在瑞芬太尼痛觉过敏发生及维持中的作用. 内容 对PICK1的结构、功能及其在瑞芬太尼痛觉过敏中的研究进行综述. 趋向 通过PICK1在瑞芬太尼痛觉过敏中的研究,为瑞芬太尼痛觉过敏的预防及治疗提供新的靶点.     

Chronic restraint stress exacerbates nociception and inflammatory response induced by bee venom in rats: the role of the P2X7 receptors

Objective: Chronic restraint stress exacerbates pain and inflammation. The present study was designed to evaluate the effect of chronic restraint stress on inflammatory pain induced by subcutaneous injection of bee venom (BV).

Methods: First, we investigated: (1) the effect of two-week restraint stress with daily 2 or 8 h on the baseline paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL) and paw circumference (PC); (2) the effect of chronic stress on the spontaneous paw-flinching reflex (SPFR), decrease in PWM, PWTL and increase in PC of the injected paw induced by BV.

Results: The results showed that (1) chronic restraint decreased significantly the PWMT and inhibited significantly the increase in PC, but had no effect on PWTL, compared with control group; (2) chronic restraint enhanced significantly BV-induced SPFR and inflammatory swelling of the injected paw. In a second series of experiments, the role of P2X7 receptor (P2X7R) in the enhancement of BV-induced inflammatory pain produced by chronic restraint stress was determined. Systemic pretreatment with P2X7R antagonist completely reversed the decrease in PWMT produced by chronic restraint, inhibited significantly the enhancement of BV-induced inflammatory pain produced by chronic restraint stress.

Conclusion: Taken together, our data indicate that chronic restraint stress-enhanced nociception and inflammation in the BV pain model, possibly involving the P2X7R.     

Neuropathic Pain models caused by damage to central or peripheral nervous system

Neuropathic Pain (NP) is a painful condition which is a direct consequence of a lesion or disease affecting the somatosensory system with symptoms like allodynia, hyperalgesia. It has complex pathogenesis as it involves several molecular signaling pathways, thus numerous reliable animal models are crucial to understand the underlying mechanism of NP and formulate effective management therapy. Some models like spinal cord injury, chronic constriction injury, spinal nerve ligation, chemotherapy induced peripheral neuropathy, diabetes-induced NP and many more are discussed. This review contains an overview of the procedures followed to induce neuropathy and specific characteristics of that particular model. Some new techniques like spared nerve ligation, have omitted the limitation of methods not presently used where complete nerve damage occurs. Since animal models provide a window to experienced symptoms and physiology and impact the translation of bench discoveries to the bedside, the reporting, interpretation and comparison of these models is necessary because slight variation in procedure of model generation can drastically alter the results. The development of novel, but rational analgesic drugs to alleviate this intractable pain demands elucidation of molecular mechanisms of NP for which different types of animal models have been established.     

痛觉过敏的中枢敏感化机制及其分子基础

痛觉过敏一向被归咎于外周伤害性感受器的敏感化。新近有证据表明，中枢神经元的敏感化和高兴奋性在痛觉过敏的发生发展中具有至关重要的作用，并主要由ＮＭＤＡ受体－ＰＣＫ－ＮＯ等一系列受体－胞内分子过程参与。中枢敏感化及其分子基础的发现可望对疼痛临床防治提供新的对策。