Janson W, Stein C
Department of Anesthesiology and Critical Care Medicine, Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany.
Curr Pharm Biotechnol. 2003 Aug;4(4):270-4. doi: 10.2174/1389201033489766.
Opioids have long been thought to act exclusively within the central nervous system. An increasing number of studies recently reported the existence of opioid receptors outside the central nervous system and therefore suggested that opioids are also able to produce analgesic effects in the periphery. Such effects are particularly prominent under painful inflammatory conditions, both in animals and in humans. During inflammatory processes, opioid receptors are transported from dorsal root ganglia towards the peripheral sensory nerve endings. At the same time, immune cells containing endogenous opioid peptides accumulate within the inflamed tissue. Environmental stimuli (e.g. stress) as well as releasing agents (e.g. corticotropin releasing factor, cytokines) can liberate these opioid peptides to interact with the neuronal opioid receptors and elicit local analgesia. The inflammation-induced activation of opioid production and the release of endogenous opioids from immune cells may lead to novel approaches for the development of peripherally acting analgesics. Clinical investigation now focuses on the development of new peripheral opioid agonists as well as on ways to stimulate the endogenous analgesic system in order to induce effective peripheral analgesia with reduced central side effects typically associated with opioids.
长期以来，人们一直认为阿片类药物仅在中枢神经系统内起作用。最近越来越多的研究报告称，中枢神经系统外存在阿片受体，因此表明阿片类药物也能够在外周产生镇痛作用。在动物和人类中，这种作用在疼痛性炎症状态下尤为显著。在炎症过程中，阿片受体从背根神经节向周围感觉神经末梢转运。与此同时，含有内源性阿片肽的免疫细胞在炎症组织中积聚。环境刺激（如压力）以及释放因子（如促肾上腺皮质激素释放因子、细胞因子）可释放这些阿片肽，使其与神经元阿片受体相互作用并引发局部镇痛。炎症诱导的阿片生成激活以及免疫细胞释放内源性阿片类物质可能会为开发外周作用的镇痛药带来新方法。目前临床研究的重点是开发新的外周阿片激动剂以及刺激内源性镇痛系统的方法，以便在减少通常与阿片类药物相关的中枢副作用的情况下诱导有效的外周镇痛。
