Department of Pharmacology, Faculty of Medicine, University of Granada, 18071 Granada, Spain; Institute of Neurosciences, Biomedical Research Center, University of Granada, Parque Tecnológico de Ciencias de la Salud, 18100 Armilla, Granada, Spain.
Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Pharmacol Res. 2018 May;131:224-230. doi: 10.1016/j.phrs.2018.02.008. Epub 2018 Feb 15.
Immune cells have a known role in pronociception, since they release a myriad of inflammatory algogens which interact with neurons to facilitate pain signaling. However, these cells also produce endogenous opioid peptides with analgesic potential. The sigma-1 receptor is a ligand-operated chaperone that modulates neurotransmission by interacting with multiple protein partners, including the μ-opioid receptor. We recently found that sigma-1 antagonists are able to induce opioid analgesia by enhancing the action of endogenous opioid peptides of immune origin during inflammation. This opioid analgesia is seen only at the inflamed site, where immune cells naturally accumulate. In this article we review the difficulties of targeting the opioid system for selective pain relief, and discuss the dual role of immune cells in pain and analgesia. Our discussion creates perspectives for possible novel therapeutic uses of sigma-1 antagonists as agents able to maximize the analgesic potential of the immune system.
免疫细胞在伤害感受中起已知作用，因为它们释放出无数的炎症致痛原，与神经元相互作用以促进疼痛信号传导。然而，这些细胞也产生具有镇痛潜力的内源性阿片肽。σ-1 受体是一种配体操纵的伴侣蛋白，通过与包括 μ-阿片受体在内的多种蛋白伴侣相互作用来调节神经递质传递。我们最近发现，σ-1 拮抗剂能够通过在炎症过程中增强免疫源性内源性阿片肽的作用来诱导阿片类镇痛。这种阿片类镇痛仅在炎症部位出现，免疫细胞自然聚集在该部位。本文综述了靶向阿片系统以实现选择性镇痛的困难，并讨论了免疫细胞在疼痛和镇痛中的双重作用。我们的讨论为 σ-1 拮抗剂作为能够最大限度地发挥免疫系统镇痛潜力的药物的可能新的治疗用途创造了前景。
