Sigma-1 receptor: A drug target for the modulation of neuroimmune and neuroglial interactions during chronic pain
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AuthorRuiz Cantero, María del Carmen; González Cano, Rafael; Tejada, Miguel Ángel; Santos Caballero, Miriam; Perazzoli, Gloria; Nieto, Francisco; Cobos del Moral, Enrique José
PainEndogenous opioid analgesiaNeuroinflammationMacrophagesMicrogliaAstrocyte
Ruiz-Cantero, M. C., González-Cano, R., Tejada, M. Á., Santos-Caballero, M., Perazzoli, G., Nieto, F. R., & Cobos, E. J. (2020). Sigma-1 receptor: A drug target for the modulation of neuroimmune and neuroglial interactions during chronic pain. Pharmacological research. [DOI: 10.1016/j.phrs.2020.105339]
SponsorshipTraining University Lecturers program (FPU) of the Spanish Ministry of Economy and Competitiveness (MINECO); Biomedical Research Institute, Hospital Clfnico Universitario in Valencia (INCLIVA); Spanish State Research Agency of MINECO SAF2016-80540-R PID2019-108691RB-100; Andalusian Regional Government CTS109; European Commission
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.