神经病理性疼痛中脊髓小胶质细胞活化的分子机制

背景 研究表明脊髓小胶质细胞活化对神经元功能调控起重要作用,并可影响脊髓背角伤害性信号的传递进而参与调控神经病理性疼痛(neuropathic pain,NP)的中枢敏化过程. 目的 探讨NP状态下脊髓小胶质细胞活化的分子机制. 内容 分别从脊髓小胶质细胞活化的胞外分子机制和胞内分子机制两方面就与此相关的研究进展作一综述. 趋向 小胶质细胞在NP中的作用将继续成为疼痛研究的热点,对小胶质细胞的深入研究可能使NP得到更为有效的治疗.     

抑制病理性疼痛相关胶质细胞活化药物的研究进展

背景 病理性疼痛的产生和持续机制十分复杂.近些年越来越多的研究者关注到脊髓胶质细胞在病理性疼痛中所发挥的作用,其中胶质细胞活化和增殖的抑制剂成为了研究的重点.目的 系统阐述胶质细胞在病理性疼痛中的作用和部分胶质细胞抑制剂的作用机制及研究进展.内容 胶质细胞不仅具有营养和支持作用,还参与了病理性疼痛,已有许多实验证实了应用胶质细胞抑制剂可以减弱胶质细胞的激活从而削弱疼痛反应.趋向 期望能为进一步的药物实验研究提供有价值的思路和借鉴.     

脊髓胶质细胞活化与病理性疼痛调节

背景 研究表明脊髓胶质细胞(星形胶质细胞和小胶质细胞)在各种病理性疼痛模型中活化,并且活化的胶质细胞在各种病理性疼痛的发生和发展中具有重要作用.目的 探讨脊髓胶质细胞在病理性疼痛调节中的作用.内容 从脊髓胶质细胞活化参与病理性疼痛调节的生理基础,脊髓胶质细胞活化及其检测,脊髓胶质细胞活化与病理性疼痛和脊髓胶质细胞参与病理性疼痛的调节机制等几方面就与此有关的研究进展进行了综述.趋向 胶质细胞将继续引起疼痛研究者的关注,因为它为临床病理性疼痛的治疗提供了新的靶点.     

星形胶质细胞与疼痛敏化调控

有关疼痛调控的中枢机制研究是当今神经科学研究领域的热点 ,但目前无论是从电生理角度 ,还是从组织学、细胞水平或分子水平 ,大多是局限于对神经元活动的研究。近年对星形胶质细胞 (astrocyte ,AST)的深入研究表明[1～ 2 ] ,其细胞膜上存在着许多离子通道、神经递质的受体 ,能够产生和释放神经活性物质 ,在慢性疼痛的形成过程中起着重要的作用。本文就星形胶质细胞在疼痛调控机制中的可能作用叙述如下。星形胶质细胞的起源、分类和功能神经系统的间质细胞或称为支持细胞有许多种 ,统称为神经胶质细胞 ,分布在外周神经系统的神经胶质细胞…     

脊髓胶质细胞的激活及其信号传递

正常情况下脊髓胶质细胞对疼痛不产生任何影响.但激活的胶质细胞及其释放的促炎症物质,特别是促炎症细胞因子有增强疼痛效应.然而胶质细胞如何被激活是一个关键问题,神经元-胶质细胞间信号分子可能在这方面具有重要作用.     

脊髓胶质细胞的激活及其信号传递

正常情况下脊髓胶质细胞对疼痛不产生任何影响.但激活的胶质细胞及其释放的促炎症物质,特别是促炎症细胞因子有增强疼痛效应.然而胶质细胞如何被激活是一个关键问题,神经元-胶质细胞间信号分子可能在这方面具有重要作用.     

反应性星形胶质细胞在慢性疼痛形成中作用的研究进展

慢性疼痛作为临床上常见的疾病, 其发病机制尚未完全阐明。多项研究表明, 在慢性疼痛发生、发展中反应性星形胶质细胞起着重要作用并且有望成为疼痛治疗的新靶标。文章对反应性星形胶质细胞在慢性疼痛形成中的作用机制及治疗前景进行总结, 以期为疼痛的研究和治疗提供新思路。     

脊髓胶质细胞活化与病理性疼痛调节

背景 研究表明脊髓胶质细胞(星形胶质细胞和小胶质细胞)在各种病理性疼痛模型中活化,并且活化的胶质细胞在各种病理性疼痛的发生和发展中具有重要作用.目的 探讨脊髓胶质细胞在病理性疼痛调节中的作用.内容 从脊髓胶质细胞活化参与病理性疼痛调节的生理基础,脊髓胶质细胞活化及其检测,脊髓胶质细胞活化与病理性疼痛和脊髓胶质细胞参与病...     

微小RNA在病理性疼痛中的作用

背景 微小RNA(microRNAs,miRNAs)是目前研究最为广泛的一类内源性非编码小分子RNA,长度范围在16～29个核苷酸之间,通过转录后调节机制调节基因的表达.最近研究发现miRNAs在不同的病理性疼痛模型中均有不同程度的表达,可能参与慢性疼痛以及急性伤害性刺激伤害感受过程的基因调节机制,调控几种与疼痛相关转录物的表达. 目的 对miRNAs在病理性疼痛中作用的研究有助于我们更清楚地了解病理性疼痛的产生和维持分子学机制,为疼痛治疗提供了新的方向. 内容 主要介绍miRNAs在炎症性痛、神经病理性痛以及疼痛相关性疾病中的表达情况,以及miRNAs在慢性病理性疼痛中的可能作用. 趋势 鉴于miRNAs在病理性疼痛的产生中具有重要作用,miRNAs将有可能作为治疗疼痛性疾病的一种新型的研究工具、生物标记和潜在的药物治疗靶点.     

神经调节蛋白1在慢性疼痛中的研究进展

背景 神经调节蛋白1 (neuregulin 1,NRG1)是一类表皮生长因子家族的成员,其在神经元及胶质细胞的生长发育及迁移等方面起着关键作用,但在成熟的神经系统及慢性疼痛中的作用却不甚清楚. 目的 阐述NRG1介导慢性疼痛的最新研究进展,并对其在疼痛中作用的研究提出展望. 内容 简述NRG1及其受体的功能以及在疼痛领域中作用的研究.趋向 NRG1通过复杂的机制参与了神经病理性疼痛的发生发展,有望为临床提供新的治疗靶点.     

Center median-parafascicular complex and pain control. Review from a neurosurgical perspective

The center median-parafascicular (CM-Pf) complex, which constitutes the major portion of the intralaminar thalamus in man, has long been known to be involved in the processing of pain under normal and pathological conditions. Yet, these 'forgotten' nuclei with their rich connectivity to other thalamic nuclei, the basal ganglia and cortical areas have received only relatively little attention over the past two decades. With regard to the recent reinterest in functional stereotactic neurosurgery as a treatment option for chronic refractory pain, the CM-Pf complex has been reconsidered as a target. This review provides a systematic overview on the current knowledge about the anatomy and connectivity of the CM-Pf complex, neurophysiological studies, and on concepts of its role in pain processing under various conditions. We also review the previous experience with ablative surgery and deep brain stimulation of the CM-Pf complex. Studies in men and experimental animals indicate that the CM-Pf complex is part of a medial pain system, which appears to be involved primarily in affective and motivational dimensions of pain. Single-unit recordings from the CM-Pf complex have shown that the activity of CM-Pf cells is modified by painful stimuli. Under pathological conditions, bursting firing patterns and altered discharge rates were found. Thalamotomies targeting at the CM-Pf complex yielded beneficial results for chronic pain, but interpretation of the results is limited. With bifocal deep brain stimulation, short-term effects of CM-Pf stimulation were superior to those of somatosensory thalamic stimulation in neuropathic pain. There is evidence, that the CM-Pf complex might also be involved in the mediation of the beneficial effects of somatosensory thalamic stimulation and periventricular grey stimulation.     

Acute and chronic pain: where we are and where we have to go

In recent years, increasing attention has been focused on the treatment of acute and chronic pain with a considerable number of publications about it. Nevertheless all the attention focused on it, the evidence of pain treatments is still unfolding, and occasionally conflicting. Hence it is still necessary that we point out our research efforts in trying to obtain a better understand of pathophysiology of pain and of real efficacy and safety of acute and chronic pain treatments. Our goal with this review is to summarize the latest research trends and the most advanced therapeutic standards for pain syndromes described in the literature, the discussion will be divided in four main topics, as these topics were treated during the SIMPAR (Study In Multidisciplinary PAin Research) meeting, held on December 2010 in Pavia: pathophysiology of pain, acute postoperative pain, opioids and pain, and chronic pain (Failed Back Surgery Syndrome). In the chapter of pathophysiology of pain we analyzed how to obtain a more personalized treatment through the study of the genetic and neurophysiological characteristics of patients and how to select the right local anesthetic according to anatomic and metabolizing patterns of patients. In acute postoperative pain we focalized our attention on the evidence supporting the use of continuous peripheral nerve blocks in the treatment of postoperative pain and in the prevention of chronic persistent post-operative pain, with a special attention in preventing side effects of regional anesthesia. We also reviewed the current evidence about the use of new very interesting modality to control postoperative pain after laparoscopy: pre-emptive nebulization of local anesthetic in abdominal cavity. As opioids are currently widely used to control chronic oncologic and non-oncologic pain, in this review we analyzed the level of evidence for their use, how to manage them better and psychological factors that can affect their success and/or determine addiction. Finally, we summarized the current evidence about Failed Back Surgery Syndrome focalizing our attention both in diagnosing it correctly and treating this syndrome with specific knowledge of the anatomic space that we have to approach and applying the possible treatments depending on pain pathophysiology and patient characteristics. In conclusion, it is important to try to personalize even better the therapy of patients with acute and chronic pain through a more accurate knowledge of anatomy, pathophysiology of pain, pharmacokinetic of pain drugs and of new device/therapies available.     

A neural model for chronic pain and pain relief by extracorporeal shock wave treatment

The paper develops a new theory of chronic pain and pain relief by extracorporeal shock wave treatment. Chronic pain without underlying anatomical disorder is looked at as a pathological control function of memory. Conditioned reflexes are considered to be engraved memory traces linking sensory input of afferent signals with motor response of efferent signals. This feature can be described by associative memory functions of the nervous system. Some conditioned reflexes may cause inappropriate or pathological reactions. Consequently, a circulus vitiosus of pain sensation and muscle and/or vessel contraction is generated when pain becomes chronic (pain spiral). The key feature is a dedicated engram responsible for a pathological (painful) reaction. The pain memory may be explained by the concept of a holographic memory model published by several authors. According to this model it is shown how nervous systems may generate and recall memory contents. The paper shows how extracorporeal shock wave treatment may reorganize pathologic memory traces, thus giving cause to real and permanent pain relief. In a generalized manner, the idea of associative memory functions may help in the understanding of conditioning as a learning process and explain extracorporeal shock wave application as an efficient treatment concept for chronic pain. This concept may open the door for new treatment approaches to chronic pain and several other disorders of the nervous system.     

High-frequency peripheral electric nerve block to treat postamputation pain

Postamputation residual limb pain is often a disabling chronic pain condition. Oftentimes, patients are left with a chronic stump pain that is refractory to current pain management modalities, such as medications, peripheral nerve blocks or denervation techniques, nerve or spinal cord stimulation, or surgical revision. Using high-frequency alternating current via a peripheral nerve cuff electrode creates a complete depolarizing nerve block, which blocks painful or unwanted nerve transmission of pain signals; the cuff is placed proximal to the neuroma at the end of the severed nerve. This article demonstrates the technique of placing a peripheral nerve cuff surgically around the peripheral nerves of patients who suffer from debilitating stump pain with lower extremity amputations. In total, 10 patients were implanted with the nerve cuff with 9 patients receiving in-clinic testing and 7 patients progressing onto long-term home-use. The average numerical rating scale pain scale for tested patients decreased from 5.7-1.4 (out of 10) after high-frequency alternating current electrical nerve block therapy with 85% of all testing sessions yielding a >50% pain reduction. Additionally, patients noted improved ability to maintain activity of daily living, as well as noted improvement of quality of life scores, and a reduction in overall pain medication use. Although the study’s initial endpoint was 90 days, we have continued to follow our implanted patients who have now reached 36 months.     

Effect of chronic nitrofurantoin on the rabbit urinary bladder

Interstitial cystitis is a pathological condition whose symptoms mimic urinary tract infection and include urgency, frequency, and moderate to severe pain. Many more women than men are affected, with antibiotic therapy being the usual first treatment approach based on symptomology. Some clinicians believe that chronic antibiotic therapy may play an etiological role in interstitial cystitis; however neither clinical nor experimental data support their opinion. The implied pathogenesis of antibiotic injury is an alteration of the bladder mucosa and its protective mucin coating to allow urine-mediated damage to the bladder wall. The purpose of this study is to evaluate rabbit urinary bladder function and morphology during chronic nitrofurantoin administration. The results demonstrate that up to twelve months of chronic nitrofurantoin administration produce no changes in 1) bacterial adherence to the rabbit bladder mucosa, 2) specific antibacterial adherence activity of the bladder mucin, and 3) ultrastructure of the mucosa, submucosa, and muscularis.     

Schmorl's nodes: current pathophysiological, diagnostic, and therapeutic paradigms

Schmorl's nodes were first described by the pathologist Christian Schmorl in 1927 as a herniation of the nucleus pulposus through the cartilaginous and bony endplate into the vertebral body. Although such lesions present most commonly as incidental findings in asymptomatic patients (or in patients with back or radicular pain due to other etiology), there have been several reports emphasizing the deleterious effects of the inflammatory response and endplate changes elicited by the herniation of for such reasons, Schmorl's nodes have been occasionally implicated in the etiology of chronic axial pain as well as in pathological osteoporotic fractures. In this article, a thorough literature review about the most relevant historical studies on Schmorl's nodes previously published is performed. Furthermore, the authors provide an overview about the recent advances in basic science research on the pathophysiology of such lesions, as well as on current diagnostic and therapeutic paradigms.     

Association between brain and low back pain

Most chronic low back pain includes elements of nociceptive pain, neuropathic pain, and nonorganic pain. We conducted screening for nonorganic pain with use of the Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP), which is simple and can be used for multidimensional assessment. Research on pain areas using functional magnetic resonance imaging (fMRI) and positron emission tomography has shown that the dopamine system contributes to the pathology of chronic low back pain. Chronic low back pain patients show decreased activation of the anterior cingulate cortex, prefrontal cortex, and nucleus accumbens. Given that both the anterior cingulate cortex and prefrontal cortex belong to the descending inhibitory system, and that the nucleus accumbens, which is involved in the dopamine system, releases μ-opioids that act to relieve pain, decreased activation in these three brain regions may be related to decreased function of the descending inhibitory system. A pathological condition that can be explained at the molecular biological level clearly exists between chronic low back pain and psychosocial factors, and investigations of a pathological condition of chronic low back pain including brain function are needed.     

肌肉骨骼慢性疼痛诊治专家共识

肌肉骨骼系统慢性疼痛是临床最常见的慢性疼痛.随着人口老龄化,慢性肌肉骨骼疼痛的总体负担将继续加重,对安全有效的疼痛管理的需求也将日益增加.由于文化、经济和监管因素不同,国际指南可能不完全适合中国病人.可用的国内指南大多只针对于药物治疗,且没有阐述中医药在肌肉骨骼系统慢性疼痛诊治中的重要作用.为了制定慢性肌肉骨骼疼痛的中...     

The role of laparoscopic adhesiolysis in chronic abdominal pain

BACKGROUND: Intraperitoneal adhesions seem to be a possible cause of chronic abdominal pain, but reports of their etiological role are controversial. Laparoscopic adhesiolysis has been proposed as treatment of choice, even tough reports of success are contradictory. The aim of our prospective study, was to determine whether laparoscopic adhesiolysis ameliorates chronic abdominal pain in patients with pathological abdominal adhesions. METHODS: Forty-five patients with chronic abdominal pain, lasting for more than 6 months, without abnormal findings other than pathological intraperitoneal adhesions found at laparoscopy, underwent laparoscopic adhesiolysis. RESULTS: Forty-one patients (91.1%) were available for follow-up after an average time interval of 18 months (range: 12-41 months): 24 patients (58.5%) were free from abdominal pain; 10 (24.4%) reported significant amelioration of pain, while 7 (17.1%) patients had no amelioration. CONCLUSIONS: Laparoscopy is an efficient means of assessing patients with chronic abdominal pain, and laparoscopic adhesiolysis cures or ameliorates. Chronic abdominal pain in more than 80% of patients.     

Devices for the relief and evaluation of pain: preface and comments

Pain is the most popular complaint since the appearance of the human on earth, a very unpleasant feeling sometimes difficult to be treated. Therefore, we have many patients who complain of pain in our hospitals or clinics. When a patient with pain visits our institution, first of all, we must evaluate the grade of pain, and then start to treat the pain of the patient. Of course, we have many devices available to treat the patient with pain. In the following special articles, device for evaluation of pain, spinal stimulation device, device for electrical current therapy (ECT), LASER device for chronic and acute pain, epiduroscopy for lumbago, as well as disposable infusion pump for postoperative pain and cancer pain are described. The mechanism of pain may be understood by patients themselves. However, devices in these articles are very useful for the treatment of pain, especially intractable pain. I feel very happy if these articles contribute greatly for the treatment of patients with pain.