Varrassi Giustino, Fusco Mariella, Skaper Stephen D, Battelli Daniele, Zis Panagiotis, Coaccioli Stefano, Pace Maria Caterina, Paladini Antonella
Department of Anesthesia and Pain Medicine, University of L'Aquila, L'Aquila, Italy.
Center for Medical Documentation and Information, Epitech, Padua, Italy.
Pain Ther. 2018 Jun;7(1):59-75. doi: 10.1007/s40122-018-0094-9. Epub 2018 Mar 28.
Chronic pain is an important health and social problem. Misuse and abuse of opioids in chronic non-cancer pain management seem to be a huge problem, in some countries. This could probably affect the normal use of such analgesics in patients in need of them. Basic and clinical researches should find the solution to mitigate the potential damage. Dysregulation of mast cell and microglia activation plays an important role in the pathogenesis and management of chronic pain. Persistent mast cell activation sensitizes nociceptors and initiates central nervous system inflammatory processes, involving microglial cell activation and sensitization of spinal somatosensory neurons. Exposure of mast cells and microglia to opioids is well known to provoke activation of these non-neuronal immune cell populations, thereby contributing to an exacerbation of pro-inflammatory and pro-nociceptive processes and promoting, over the long-term, opioid-induced hyperalgesia and tolerance. This review is intended to provide the reader with an overview of the role for these non-neuronal cells in opioid-induced chronic pain and tolerance as a consequence of prolonged exposure to these drugs. In addition, we will examine a potential strategy with the aim to modulate opioid-induced over-activation of glia and mast cells, based on endogenous defense mechanisms and fatty acid amide signaling molecules.
慢性疼痛是一个重要的健康和社会问题。在一些国家，慢性非癌性疼痛管理中阿片类药物的误用和滥用似乎是一个巨大的问题。这可能会影响到有需要的患者对这类镇痛药的正常使用。基础研究和临床研究应找到减轻潜在损害的解决办法。肥大细胞和小胶质细胞激活失调在慢性疼痛的发病机制和管理中起着重要作用。持续的肥大细胞激活会使伤害感受器敏感化，并启动中枢神经系统炎症过程，包括小胶质细胞激活和脊髓体感神经元敏感化。众所周知，肥大细胞和小胶质细胞暴露于阿片类药物会引发这些非神经元免疫细胞群体的激活，从而导致促炎和促痛觉过程加剧，并长期促进阿片类药物诱导的痛觉过敏和耐受性。本综述旨在为读者概述这些非神经元细胞在长期接触这些药物导致的阿片类药物诱导的慢性疼痛和耐受性中的作用。此外，我们将基于内源性防御机制和脂肪酸酰胺信号分子，研究一种潜在策略，旨在调节阿片类药物诱导的胶质细胞和肥大细胞过度激活。
