具有抗超敏作用的镇痛剂奈福泮对大鼠手术后长期疼痛易感性的预防

背景 与外科手术有关的组织损伤经常产生外周及中枢敏化,这可以延长刺激,导致手术后剧烈疼痛.矛盾的是,阿片类药物的应用,对于手术后疼痛管理是必须的,但可能诱导疼痛敏化,导致手术后疼痛增强,并增加发展成为慢性疼痛的风险.我们通过评价3周后未损伤对侧足底的炎症反应所诱导的痛觉超敏,研究大鼠足底的手术切皮是否可以增加长期疼痛易...     

预先镇痛——通过防止中枢敏感性增高来处理术后疼痛

神经系统对外周组织损伤表现为两种反应:①外周敏感性增高,即外周传入纤维末梢伤害感受器阈值降低;②中枢敏感性增高,脊神经元兴奋性呈活动依赖性增高,痛阈降低,从而造成术后的痛觉高敏状态。术前使用局麻或阿片类药来防止中枢敏感性增高,能有效地减轻术后疼痛。但由于术中组织损伤引起的炎性反应可使术后中枢敏感性增高,仅仅局限于术前或术中的处理对很多病人可能尚嫌不足。因此,为了减轻病人疼痛,又不致损伤生理伤害感受器的预警作用,理想的方法是在术前、术中及术后均予以处理以防止痛觉高敏状态的形成。     

miRNA与神经病理性疼痛的关系研究进展

<正>疼痛按持续时间长短可分为急性和慢性疼痛:急性疼痛持续时间通常短于1个月,常与手术创伤、组织损伤及疾病状态有关,其机制主要与局部组织损伤和炎症导致疼痛性介质(P物质等)大量产生和集聚在外周神经末梢有关。而慢性疼痛则通常持续3个月以上,在原发病或组织损伤愈合后依然持续存在[1]。神经病理性疼痛(neuropathic pain,NPP)属一种慢性疼痛,表现为自发性疼痛、痛觉过敏、异常疼痛和     

脊髓N-甲基-D-天冬氨酸受体在大鼠慢性内脏痛中的作用

内脏痛觉过敏的产生涉及外周敏化和中枢敏化两种机制.中枢敏化在内脏痛的发生发展过程中起重要作用[1].中枢敏化的形成涉及多种神经递质受体,尤其是脊髓N-甲基-D-天冬氨酸(NMDA)受体在组织损伤和炎症导致躯体痛的中枢敏化形成中起重要作用[2,3].有研究表明,脊髓NMDA受体参与了急性内脏痛的发生[4,5],而其在慢性内脏痛中的作用尚不明确.本研究拟评价脊髓NMDA受体在大鼠慢性内脏痛中的作用.     

损伤反应和术后疼痛的预防

国际疼痛研究会(IASP)急性疼痛组以预防性措施为重点正在广泛研究处理急性疼痛的方法。随着公众对疼痛治疗的了解和期望,医务人员对疼痛处理的训练、知识和实践也必须相应改变,以求减少不必要的术后疼痛和损伤反应。防止术后疼痛的理论基础已有大量资料证实,组织损伤能使外周痛觉感受器敏感化,甚至产生超敏(hypersensitivity)。近年又证实某些炎性反应的组织、血液和神经成分能在外周水平引起原发性或继发性“过痛”(hypcralgcsia),所以就有可能寻求到作用于外周痛觉传入神经元的新措施和镇痛药,     

MAPK/ERK信号转导通路与疼痛敏化调控

初级感觉神经元的外周敏化和脊髓后角的中枢敏化是病理性疼痛的主要机制。多种伤害性刺激能使细胞外信号调节激酶（ERK）在背根神经节和脊髓后角中特异性激活和表达增多,这种现象能被MEK特异性抑制剂所明显阻断,并能使明显减弱伤害性刺激所导致的痛觉过敏和异常痛觉,可见,MAPK／ERK信号转导通路在疼痛敏化调控方面发挥着重要作用。ERK激活（P—ERK）后可调控一些基因表达和磷酸化一系列底物,参与疼痛敏化凋控,并且可能是通过长时程增强方式来改变突触可塑性来实现。随着研究深入,有望为疼痛治疗提供新的靶位。     

丝裂原活化蛋白激酶家族与病理性疼痛

病理性疼痛包括炎性痛和神经病理性痛。炎性痛是由创伤、细菌或病毒感染及外科手术等引起的外周组织损伤导致的炎症而引起的疼痛;神经病理性疼痛是由于外周或中枢神经系统的直接损伤或功能紊乱引起的疼痛,其共同的临床表现有自发性疼痛、痛觉过敏、触诱发痛等。许多脊髓或高级中枢神经病理生理的改变都可引起或参与病理性神经痛的形成。目前的研究认为,脊髓背角神经元及脊髓胶质细胞丝裂原活化蛋白激酶家族活化与病理性疼痛有关[1,2]。现就MAPKs在病理性疼痛的发生、发展过程中所起的作用作一综述。1 MAPKsMAPKs在所有真核细胞中均有表…     

不同剂量布托啡诺超前镇痛应用于腹腔镜胆囊切除术的效果

中枢敏化可对疼痛产生不利影响,故有人主张在手术开始前就采取措施,以阻滞伤害性感受器,从而达到防止中枢敏化、减轻术后疼痛的目的[1].这种方法被称之为"超前镇痛".布托啡诺主要激动k受体,而作为μ受体激动-拮抗     

活性氧在持续性疼痛中枢敏化中作用机制研究新进展

背景 中枢敏化是持续性疼痛的重要基础机制.活性氧(reactive oxygen species,ROS)为正常细胞代谢的副产品,其表达增加可诱发脊髓中枢敏化参与持续性疼痛.目的 分析总结ROS在持续性疼痛中枢敏化中作用机制的新近文献资料.内容 ROS作为中枢敏化过程的功能性信使分子参与持续性疼痛并起关键作用,目前认为其作用机制可能与谷氨酸能通路增强、神经炎症发生、γ-氨基丁酸释放减少和瞬态感受器电位阳离子通道,子类V,成员1 (transient receptor potential cation channel,subfamily V,member 1,TRPV1)活化等有关.趋向 深入研究ROS在中枢敏化中的作用机制将有助于为持续性疼痛提供坚实的治疗策略.     

NSAIDs对抗脊髓伤害传递的机理

非甾体抗炎药物(NSAIDs)的镇痛作用是由于抑制了外周前列腺素的合成。组织损伤与局部释放不同的介质有关,包括5-羟色胺、缓激肽、组胺、P物质和前列腺素。目前普遍接受的结论认为:前列腺素不是重要的疼痛介质,但可通过敏化感觉神经末端释放其它介质,引起痛觉过敏。 已证明NSAIDs在体内外均可抑制前列     

Neural mechanisms underlying deafferentation pain: a hypothesis from a neuroimaging perspective

Deafferentation pain following nerve injury annoys patients, and its management is a challenge in clinical practice. Although the mechanisms underlying deafferentation pain remain poorly understood, progress in the development of multidimensional neuroimaging techniques is casting some light on these issues. Deafferentation pain likely results from reorganization of the nervous system after nerve injury via processes that interact with the substrates for pain perception (the pain matrix). Therapeutic effects of motor cortex stimulation on deafferentation pain suggest that the core mechanisms underlying deafferentation pain also interact with the motor system. Therefore, simultaneous neuroimaging and brain stimulation, an emerging neuroimaging technique, was developed to investigate complicated interactions among motor, somatosensory, and pain systems. In healthy participants, parts of the pain matrix (the anterior cingulate cortex, parietal operculum, and thalamus) show activity during both somatosensory stimulation and brain stimulation to the motor cortex. This finding indicates that motor, somatosensory, and pain systems communicate among each other via the neural network. A better understanding of the plastic mechanisms influencing such cross-talk among these systems will help develop therapeutic interventions using brain stimulation and neurofeedback.     

Adjustierbare transobturatorische Schlingensysteme beim Mann

Background

In addition to artificial sphincters, male slings are recommended in the current guidelines for the treatment of persistent male stress incontinence. Today, several sling systems are available. Well-known complications of all sling systems are infections, erosion, residual urine/urinary retention, de novo urgency, and postoperative pain.

Discussion

Compared to retropubic implanted adjustable sling systems or functional slings, pain is more common after transobturatoric implantation of adjustable sling systems. Early postoperative pain is very common. In contrast, persistent pain is rare. However, the treatment of persistent pain is a large challenge for urologists and patients. There are no recommendations for diagnostic workup or treatment.

Results

After pain classification, pain management should be started with nonsteroidal anti-inflammatory drugs and/or tricyclic antidepressive agents, if necessary treatment escalation with a weak opioid and if not effective interventional procedures should be performed. Sling explantation is only necessary in rare cases.     

Le contrôle central de la douleur

We describe the anatomic and physiological components involved in pain physiology, with the goal of providing readers with the background information needed to understand central pain control mechanisms. These include spinal segmental controls, supraspinal excitatory and inhibitory controls, and diffuse noxious inhibitory controls. Pain is a subjective sensation produced by an emotionally unpleasant experience considered to originate in adaptive processes taking place within neuron networks located at various levels of the central nervous system. The intensity of the components of pain is influenced by the stimulus characteristics, patient-related factors, and the setting in which the stimulus occurs. The various components of pain and the psychological and neurophysiological mechanisms that underlie the affective dimension of pain are reviewed. As a conclusion, phantom pain is used to illustrate the role for physiological systems independent from those involved in the physiology of nociception and pain, such as the motor cortex. This example highlights the extreme complexity of pain and pain control systems in humans.     

Central pain control

We describe the anatomic and physiological components involved in pain physiology, with the goal of providing readers with the background information needed to understand central pain control mechanisms. These include spinal segmental controls, supraspinal excitatory and inhibitory controls, and diffuse noxious inhibitory controls (DNICs). Pain is a subjective sensation produced by an emotionally unpleasant experience considered to originate in adaptive processes taking place within neuron networks located at various levels of the central nervous system. The intensity of the components of pain is influenced by the stimulus characteristics, patient-related factors, and the setting in which the stimulus occurs. The various components of pain and the psychological and neurophysiological mechanisms that underlie the affective dimension of pain are reviewed. As a conclusion, phantom pain is used to illustrate the role for physiological systems independent from those involved in the physiology of nociception and pain, such as the motor cortex. This example highlights the extreme complexity of pain and pain control systems in humans.     

Local and regional anaesthetic techniques in wound management

Adequate pain control is vital in perioperative care. Pain affects respiratory and cardiovascular function with knock-on effects on many other organs and systems. Surgery is also recognized as one of the most frequent causes of chronic pain with surgical approach and level of pain experienced being modifiable risk factors for the development of chronic post-surgical pain.     

Selection of implantable narcotic delivery systems

Intraspinal narcotics have dramatically influenced the way pain of malignant origin is managed. There has been a rapid acceptance of this modality within the anesthesia community to treat a wide variety of cancer pain problems. In tandem the development of various implantable narcotic delivery systems has complemented and facilitated the expanded role of intraspinal narcotics in the treatment of cancer pain. Appropriate patient selection is crucial if optimal results are to be achieved. Factors to be considered in patient selection should include the results of the preimplantation spinal narcotic trial, infection trial, infection and local conditions, hematologic status, physiologic and behavioral abnormalities, cost, patient support systems and life expectancy. By interfacing these factors with the unique profiles that each of the five types of implantable narcotic delivery systems offer, improved results both in terms of pain relief and patient satisfaction can be expected.     

Validation of three paediatric pain scores for use by parents

Twenty children undergoing general surgery and 20 children undergoing otorhinolaryngological surgery were simultaneously assessed on two occasions by a doctor and a parent using three pain scoring systems. The pain scoring systems used were the Objective Pain Score, a four point numerical score and a 100 mm visual analogue scale. There was a high correlation between the scores given by the doctor and by the parents for all three scoring systems with parents consistently giving slightly higher scores than the doctor. The correlation coefficients for parental and medical pain scores in recovery were 0.77 for the Objective Pain Score, 0.70 for the four point numerical score and 0.69 for the visual analogue scale (p < 0.01). At 1 h after leaving the recovery area the correlation coefficients were 0.81, 0.80 and 0.73 respectively (p < 0.01). These results suggest that parental scoring of pain in children will be useful in future audit and research of analgesic regimens, particularly in day-case surgery.     

Serotonergic activity in man as a function of pain, pain mechanisms, and depression

Lumbar cerebrospinal fluid levels of 5-hydroxyindoleacetic acid, which are used as indicators of central nervous system serotonergic neuronal activity, were significantly higher in 67 patients with chronic pain and in 32 patients with acute pain (23.6 +/- 3.3 and 23.1 +/- 3.8, respectively) than in 30 patients (8.8 +/- 1.7) who had no pain. However, there was no correlation between levels of 5-hydroxyindoleacetic acid in patients with chronic or acute pain, nor between groups of patients with chronic pain whose pain mechanisms were of psychogenic, sympathetic, somatic, or central origin, based on their responses to differential spinal block; there was also no correlation between levels of depression, as evaluated by the Zung scale, in patients with different types of chronic pain, even though all of these patients were depressed. The elevated levels of 5-hydroxyindoleacetic acid in the depressed patients with chronic pain are not consistent with previous studies on the etiology and types of chronic pain. As recent research indicates that the perception of pain may be modulated by endogenous analgesic systems involving enkephalin and serotonin (5-HT), this study was undertaken to clarify the association between 5-HT activity and nociception. Our findings did show a link between acute noxious stimulation and central increases in serotonergic activity. However, we could not differentiate between pain mechanisms and degree of depression. Our studies did indicate that, because of both the persistence of pain complaints and the increased levels of brain 5-HT activity, the endogenous analgesic systems are not totally effective as natural inhibitors of pain. Furthermore, the increased depression and continued pain in the presence of elevated 5-HT activity in patients with chronic pain may represent a tolerance or decreased responsiveness to 5-HT.     

Double-blind testing fails to confirm analgesic response to extradural morphine

We report two patients with chronic non-malignant pain in whom morphine given intravenously via a patient-controlled analgesia system produced partial pain relief but was accompanied by severe side effects. Open administration of epidural morphine resulted in complete pain relief with minimal side effects and the patients were considered as candidates for implanted opioid delivery systems. However, when the epidural morphine was given in a double-blind and placebo-controlled manner, morphine did not produce greater analgesia than placebo and no dose-response relationship was seen. These cases show that careful investigation is necessary before proceeding to implanted systems and that changing the route did not improve the analgesia:side effect balance for morphine in these patients.     

Neurophysiologic and pathologic aspects of acute and chronic pain.

Acute pain produced by disease or injury is the net effect of highly complex interactions of various neural systems and psychological factors. Through the interaction of the afferent systems and neocortical processes, the individual is provided perceptual information regarding location, magnitude, and spatial and temporal properties of the noxious stimulus that activates motivational tendencies toward escape or attack and permits analysis of multimodal information, past experience, and probability of outcome of different response strategies. In contrast, chronic pain is a malefic force that taxes the physical, emotional, and economic resources of the patient, his famiily, and society. Moreover, chronic pain is characterized by physiological affective and behavioral responses that are quite different than those of acute pain. The clinician must keep these differences in mind in order to provide patients with optimal relief of their pain.