Spetea Mariana
Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, Austria.
Curr Pharm Des. 2013;19(42):7382-90. doi: 10.2174/13816128113199990363.
Interest in opioid drugs like morphine, as the oldest and most potent pain-killing agents known, has been maintained through the years. One of the most frequent chronic pain sensations people experience is associated with pathological conditions of the musculoskeletal system. Chronic musculoskeletal pain is a major health problem, and an adequate management requires understanding of both peripheral and central components, with more attention drawn to the former. Intense experimental and clinical research activities resulted in important knowledge on the mechanisms and functions of the endogenous opioid system located in the periphery. This review describes the occurrence and distribution of endogenous opioids and their receptors in the musculoskeletal system, and their role in pain control in musculoskeletal disorders, such as rheumatoid arthritis and osteoarthritis. Using different techniques, including immunohistochemistry, electron microscopy or radioimmunoassay, expression of enkephalins, dynorphin, β-endorphin, and endomorphins was demonstrated in musculoskeletal tissues of animals and humans. Localization of opioid peptides was found in synovial membrane, periosteum, bone and bone marrow, loose connective tissue, the paratenon and musculotendinous junction of the achilles tendon. Animal and human studies have also demonstrated expression of µ, δ and κ opioid receptor proteins in musculoskeletal tissues using radioligand binding assays, autoradiography, electrophysiology, immunohistochemistry and Western blotting. Opioid receptor gene expression was reported based on polymerase chain reaction and in situ hybridization techniques. Combining morphological and quantitative approaches, important evidence that the musculoskeletal apparatus is equipped with a peripheral opioid system is provided. Demonstration of the occurrence of an endogenous opioid system in bone and joint tissues represents an essential step for defining novel pharmacological strategies to attain peripheral control of pain in musculoskeletal disorders.
多年来，人们一直对吗啡等阿片类药物保持着兴趣，因为它们是已知最古老、最有效的止痛剂。人们最常经历的慢性疼痛感觉之一与肌肉骨骼系统的病理状况有关。慢性肌肉骨骼疼痛是一个主要的健康问题，充分的管理需要了解外周和中枢成分，其中对外周成分的关注更多。大量的实验和临床研究活动带来了关于外周内源性阿片系统机制和功能的重要知识。这篇综述描述了内源性阿片及其受体在肌肉骨骼系统中的存在和分布，以及它们在类风湿性关节炎和骨关节炎等肌肉骨骼疾病疼痛控制中的作用。使用包括免疫组织化学、电子显微镜或放射免疫分析在内的不同技术，在动物和人类的肌肉骨骼组织中证实了脑啡肽、强啡肽、β-内啡肽和内吗啡肽的表达。在滑膜、骨膜、骨骼和骨髓、疏松结缔组织、腱旁组织和跟腱的肌腱结合处发现了阿片肽的定位。动物和人体研究还使用放射性配体结合分析、放射自显影、电生理学、免疫组织化学和蛋白质印迹法证明了μ、δ和κ阿片受体蛋白在肌肉骨骼组织中的表达。基于聚合酶链反应和原位杂交技术报道了阿片受体基因表达。结合形态学和定量方法，提供了重要证据表明肌肉骨骼器官配备了外周阿片系统。证明骨和关节组织中存在内源性阿片系统是确定在肌肉骨骼疾病中实现外周疼痛控制的新药理学策略的关键一步。
