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胃肠道相关疼痛的心理神经免疫学研究方法

Psychoneuroimmunological approach to gastrointestinal related pain.

作者信息

Toljan Karlo, Vrooman Bruce

机构信息

Department of Pathophysiology, University of Zagreb School of Medicine, Kispaticeva 12, Zagreb 10 000, Croatia.

Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, 1 Medical Center Dr, Lebanon, NH 03766, USA.

出版信息

Scand J Pain. 2017 Oct;17:431-443. doi: 10.1016/j.sjpain.2017.10.010. Epub 2017 Nov 6.

Abstract

BACKGROUND AND PURPOSE (AIMS): Psychoneuroimmunology is both a theoretical and practical field of medicine in which human biology and psychology are considered an interconnected unity. Through such a framework it is possible to elucidate complex syndromes in gastrointestinal related pain, particularly chronic non-malignant. The aim is to provide insight into pathophysiological mechanisms and suggest treatment modalities according to a comprehensive paradigm. The article also presents novel findings that may guide clinicians to recognize new targets or scientists to find new research topics.

METHODS

A literature search of 'PubMed' and 'Google Scholar' databases was performed. Search terms included: 'Visceral pain', 'Psychoneuroimmunology', 'Psychoneuroimmunology and pain', 'Pain in GI system', 'GI related pain', 'Pain and microbiota', 'Enteric nervous system', 'Enteric nervous system and inflammation', 'CNS and pain', 'Inflammation and pain in GI tract', 'Neurogastroenterology', 'Neuroendocrinology', 'Immune system in GI pain'. After searching and reading sources deemed recent and relevant, a narrative review was written with a tendency to discriminate the peripheral, intermediate, and central pathophysiological mechanisms or treatment targets.

RESULTS

Recent evidence point out the importance of considering the brain-gut axis as the main connector of the central and peripheral phenomena encountered in patients suffering from chronic non-malignant gastrointestinal related pain. This axis is also a prime clinical target with multiple components to be addressed in order for therapy to be more effective. Patients suffering from inflammatory bowel disease or functional gastrointestinal disorders represent groups that could benefit most from the proposed approach.

CONCLUSIONS (BASED ON OUR FINDINGS): Rather than proceeding with established allopathic single-target central or peripheral treatments, by non-invasively modulating the brain-gut axis components such as the psychological and neuroendocrinological status, microbiota, enteric nervous system, or immune cells (e.g. glial or mast cells), a favourable clinical outcome in various chronic gastrointestinal related pain syndromes may be achieved. Clinical tools are readily available in forms of psychotherapy, prebiotics, probiotics, nutritional advice, and off-label drugs. An example of the latter is low-dose naltrexone, a compound which opens the perspective of targeting glial cells to reduce neuroinflammation and ultimately pain.

IMPLICATIONS (OUR OPINION ON WHAT OUR FINDINGS MEAN): Current findings from basic science provide sound mechanistic evidence and once entering clinical practice should yield more effective outcomes for patients. In addition to well-established pharmacotherapy comprised notably of anti-inflammatories, antibiotics, and proton-pump inhibitors, valid treatment strategies may contain other options. These disease modulating add-ons include probiotics, prebiotics, food supplements with anti-inflammatory properties, various forms of psychotherapy, and low-dose naltrexone as a glial modulator that attenuates neuroinflammation. Clearly, a broader and still under exploited set of evidence-based tools is available for clinical use.

摘要

背景与目的(目标):心理神经免疫学是医学领域中一个兼具理论性与实践性的学科,它将人类生物学和心理学视为一个相互关联的统一体。通过这样一个框架,能够阐明胃肠道相关疼痛,尤其是慢性非恶性疼痛中的复杂综合征。其目的是深入了解病理生理机制,并依据一个全面的范式提出治疗方式。本文还呈现了一些新发现,这些发现可能会引导临床医生识别新的靶点,或者为科学家提供新的研究课题。

方法

对“PubMed”和“谷歌学术”数据库进行文献检索。检索词包括:“内脏痛”“心理神经免疫学”“心理神经免疫学与疼痛”“胃肠道系统疼痛”“胃肠道相关疼痛”“疼痛与微生物群”“肠神经系统”“肠神经系统与炎症”“中枢神经系统与疼痛”“胃肠道炎症与疼痛”“神经胃肠病学”“神经内分泌学”“胃肠道疼痛中的免疫系统”。在检索并阅读了近期且相关的资料后,撰写了一篇叙述性综述,倾向于区分外周、中间和中枢的病理生理机制或治疗靶点。

结果

近期证据指出,将脑 - 肠轴视为慢性非恶性胃肠道相关疼痛患者所出现的中枢和外周现象的主要连接体具有重要意义。该轴也是一个主要的临床靶点,为使治疗更有效,需要解决多个组成部分。患有炎症性肠病或功能性胃肠疾病的患者群体可能会从所提出的方法中获益最多。

结论(基于我们的研究结果):相较于采用既定的对抗疗法单靶点中枢或外周治疗方法,通过非侵入性地调节脑 - 肠轴的组成部分,如心理和神经内分泌状态、微生物群、肠神经系统或免疫细胞(如神经胶质细胞或肥大细胞),可能会在各种慢性胃肠道相关疼痛综合征中取得良好的临床效果。临床工具以心理治疗、益生元、益生菌、营养建议和非处方药的形式 readily available(此处原文有误,应是readily available,意为“ readily available”)。后者的一个例子是低剂量纳曲酮,这种化合物为靶向神经胶质细胞以减轻神经炎症并最终缓解疼痛开辟了前景。

启示(我们对研究结果意义的看法):基础科学的当前发现提供了可靠的机制证据,一旦应用于临床实践,应为患者带来更有效的治疗效果。除了由抗炎药、抗生素和质子泵抑制剂显著组成的成熟药物治疗外,有效的治疗策略可能还包含其他选择。这些疾病调节附加措施包括益生菌、益生元、具有抗炎特性的食品补充剂、各种形式的心理治疗以及作为神经胶质调节剂可减轻神经炎症的低剂量纳曲酮。显然,有一套更广泛且仍未充分利用的循证工具可供临床使用。

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