Department of Pharmacology, and Neurosciences Institute (Biomedical Research Center), University of Granada, Granada, Spain; Biosanitary Research Institute ibs.GRANADA, Granada, Spain.
Department of Pharmacology, and Neurosciences Institute (Biomedical Research Center), University of Granada, Granada, Spain; INCLIVA Health Research Institute, Valencia, Spain.
Pharmacol Res. 2021 Jan;163:105339. doi: 10.1016/j.phrs.2020.105339. Epub 2020 Dec 1.
Immune and glial cells play a pivotal role in chronic pain. Therefore, it is possible that the pharmacological modulation of neurotransmission from an exclusively neuronal perspective may not be enough for adequate pain management, and the modulation of complex interactions between neurons and other cell types might be needed for successful pain relief. In this article, we review the current scientific evidence for the modulatory effects of sigma-1 receptors on communication between the immune and nervous systems during inflammation, as well as the influence of this receptor on peripheral and central neuroinflammation. Several experimental models of pathological pain are considered, including peripheral and central neuropathic pain, osteoarthritic, and cancer pain. Sigma-1 receptor inhibition prevents peripheral (macrophage infiltration into the dorsal root ganglion) and central (activation of microglia and astrocytes) neuroinflammation in several pain models, and enhances immune-driven peripheral opioid analgesia during painful inflammation, maximizing the analgesic potential of peripheral immune cells. Therefore, sigma-1 antagonists may constitute a new class of analgesics with an unprecedented mechanism of action and potential utility in several painful disorders.
免疫细胞和神经胶质细胞在慢性疼痛中起着关键作用。因此，仅从神经元的角度对神经递质传递进行药理学调节可能不足以进行充分的疼痛管理，可能需要调节神经元和其他细胞类型之间的复杂相互作用，以实现成功的疼痛缓解。在本文中，我们回顾了目前关于 sigma-1 受体在炎症期间调节免疫和神经系统之间通讯的科学证据，以及该受体对周围和中枢神经炎症的影响。考虑了几种病理性疼痛的实验模型，包括周围和中枢神经性疼痛、骨关节炎和癌症疼痛。Sigma-1 受体抑制剂可预防几种疼痛模型中的外周（巨噬细胞浸润背根神经节）和中枢（小胶质细胞和星形胶质细胞的激活）神经炎症，并增强免疫驱动的外周阿片类镇痛作用在疼痛性炎症期间，最大限度地发挥外周免疫细胞的镇痛潜力。因此，sigma-1 拮抗剂可能构成一类具有前所未有的作用机制的新型镇痛药，在几种疼痛性疾病中有潜在的应用价值。
